Prevention of dialysis disequilibrium syndrome in children with advanced uremia with a structured hemodialysis protocol: A quality improvement initiative study.

BACKGROUND: Dialysis disequilibrium syndrome (DDS) is a rare but significant concern in adult and pediatric patients undergoing dialysis initiation with advanced uremia or if done after an interval. It is imperative to gain insights into the epidemiological patterns, pathophysiological mechanisms, and preventive strategies aimed at averting the onset of this ailment. DESIGN: Prospective observational quality improvement initiative cohort study. SETTING AND PARTICIPANTS: A prospective single-center study involving 50 pediatric patients under 18 years recently diagnosed with chronic kidney disease stage V with blood urea ≥200 mg/dL, admitted to our tertiary care center for dialysis initiation from January 2017 to October 2023. QUALITY IMPROVEMENT PLAN: A standardized protocol was developed and followed for hemodialysis in pediatric patients with advanced uremia. This protocol included measures such as lower urea reduction ratios (targeted at 20%-30%) with shorter dialysis sessions and linear dialysate sodium profiling. Prophylactic administration of mannitol and 25% dextrose was also done to prevent the incidence of dialysis disequilibrium syndrome. MEASURES: Incidence of dialysis disequilibrium syndrome and severe dialysis disequilibrium syndrome, mortality, urea reduction ratios (URRs), neurological outcome at discharge, and development of complications such as infection and hypotension. Long-term outcomes were assessed at the 1-year follow-up including adherence to dialysis, renal transplantation, death, and loss to follow-up. RESULTS: The median serum creatinine and urea levels at presentation were 7.93 and 224 mg/dL, respectively. A total of 20% of patients had neurological symptoms attributable to advanced uremia at the time of presentation. The incidence of dialysis disequilibrium syndrome was 4% (n = 2) with severe dialysis disequilibrium syndrome only 2% (n = 1). Overall mortality was 8% (n = 4) but none of the deaths were attributed to dialysis disequilibrium syndrome. The mean urea reduction ratios for the first, second, and third dialysis sessions were 23.45%, 34.56%, and 33.50%, respectively. The patients with dialysis disequilibrium syndrome were discharged with normal neurological status. Long-term outcomes showed 88% adherence to dialysis and 38% renal transplantation. LIMITATIONS: This study is characterized by a single-center design, nonrandomized approach, and limited sample size. CONCLUSIONS: Our structured protocol served as a framework for standardizing procedures contributing to low incidence rates of dialysis disequilibrium syndrome.

Assessment of South Asian Pediatric Acute Kidney Injury: Epidemiology and Risk Factors (ASPIRE)-a prospective study on "severe dialysis dependent pediatric AKI".

BACKGROUND: Pediatric acute kidney injury (AKI) is a global health concern with an associated mortality risk disproportionately pronounced in resource-limited settings. There is a pertinent need to understand the epidemiology of pediatric AKI in vulnerable populations. Here, we proposed a prospective study to investigate the epidemiology and associated risk factors of "severe dialysis dependent AKI" in children among South Asian nations which would be the first and largest of its kind. METHODS: The ASPIRE study (part of PCRRT-ICONIC Foundation initiative) is a multi-center, prospective observational study conducted in South Asian countries. All children and adolescents ≤ 18 years of age who required dialysis for AKI in any of the collaborating medical centers were enrolled. Data collection was performed until one of the following endpoints was observed: (1) discharge, (2) death, and (3) discharge against medical advice. RESULTS: From 2019 to 2022, a total of 308 children with severe AKI were enrolled. The mean age was 6.17 years (63% males). Secondary AKI was more prevalent than primary AKI (67.2%), which predominantly occurred due to infections, dehydration, and nephrotoxins. Common causes of primary AKI were glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, and obstructive uropathy. Shock, need for ventilation, and coagulopathy were commonly seen in children with severe AKI who needed dialysis. The foremost kidney replacement therapy used was peritoneal dialysis (60.7%). The mortality rate was 32.1%. CONCLUSIONS: Common causes of AKI in children in South Asia are preventable. Mortality is high among these children suffering from "severe dialysis dependent AKI." Targeted interventions to prevent and identify AKI early and initiate supportive care in less-resourced nations are needed.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Switching from continuous veno-venous hemodiafiltration to intermittent sustained low-efficiency daily hemodiafiltration (SLED-f) in pediatric acute kidney injury: A prospective cohort study.

INTRODUCTION: Continuous kidney replacement therapy (CKRT) is the preferred modality in critically ill children with acute kidney injury. Upon improvement, intermittent hemodialysis is usually initiated as a step-down therapy, which can be associated with several adverse events. Hybrid therapies such as Sustained low-efficiency daily dialysis with pre-filter replacement (SLED-f) combines the slow sustained features of a continuous treatment, ensuring hemodynamic stability, with similar solute clearance along with the cost effectiveness of conventional intermittent hemodialysis. We examined the feasibility of using SLED-f as a transition step-down therapy after CKRT in critically ill pediatric patients with acute kidney injury. METHODS: A prospective cohort study was conducted in children admitted to our tertiary care pediatric intensive care units with multi-organ dysfunction syndrome including acute kidney injury who received CKRT for management. Those patients receiving fewer than two inotropes to maintain perfusion and failed a diuretic challenge were switched to SLED-f. RESULTS: Eleven patients underwent 105 SLED-f sessions (mean of 9.55 +/- 4.90 sessions per patient), as a part of step-down therapy from continuous hemodiafiltration. All (100%) our patients had sepsis associated acute kidney injury with multiorgan dysfunction and required ventilation. During SLED-f, urea reduction ratio was 64.1 +/- 5.3%, Kt/V was 1.13 +/- 0.1, and beta-2 microglobulin reduction was 42.5 +/-4%. Incidence of hypotension and requirement of escalation of inotropes during SLED-f was 18.18%. Filter clotting occurred twice in one patient. CONCLUSION: SLED-f is a safe and effective modality for use as a transition therapy between CKRT and intermittent hemodialysis in children in the PICU.

Validation of the STARZ neonatal acute kidney injury risk stratification score in an independent prospective cohort.

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7-19) vs. 7 (5-10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74-14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934-0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates.

Risk factors and outcomes of neonates with acute kidney injury needing peritoneal dialysis: Results from the prospective TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) study.

BACKGROUND: Acute kidney injury (AKI) is common in neonates admitted to neonatal intensive care units (NICUs). There is a need to have prospective data on the risk factors and outcomes of acute peritoneal dialysis (PD) in neonates. The use of kidney replacement therapy in this population compared to older populations has been associated with worse outcomes (mortality rates 17-24%) along with a longer stay in the NICU and/or hospital. METHODS: The following multicentre, prospective study was derived from the TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) database, assessing all admitted neonates ≤28 days who received intravenous fluids for at least 48 h. The following neonates were excluded: death within 48 h, presence of any lethal chromosomal anomaly, requirement of congenital heart surgery within the first 7 days of life and those receiving only routine care in nursery. Demographic data (maternal and neonatal) and daily clinical and laboratory parameters were recorded. AKI was defined according to the Neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of the included 1600 neonates, a total of 491 (30.7%) had AKI. Of these 491 neonates with AKI, 44 (9%) required PD. Among neonates with AKI, the odds of needing PD was significantly higher among those with significant cardiac disease (odds ratio (95% confidence interval): 4.95 (2.39-10.27); p < 0.001), inotropes usage (4.77 (1.98-11.51); p < 0.001), severe peripartum event (4.37 (1.31-14.57); p = 0.02), requirement of respiratory support in NICU (4.17 (1.00-17.59); p = 0.04), necrotising enterocolitis (3.96 (1.21-13.02); p = 0.03), any grade of intraventricular haemorrhage (3.71 (1.63-8.45); p = 0.001), evidence of fluid overload during the first 12 h in NICU (3.69 (1.27-10.70); p = 0.02) and requirement of resuscitation in the delivery room (2.72 (1.45-5.12); p = 0.001). AKI neonates with PD as compared to those without PD had a significantly lower median (interquartile range) duration of stay in NICU (7 (4-14) vs. 11 (6-21) days; p = 0.004), but significantly higher mortality (31 (70.5%) vs. 50 (3.2%); p < 0.001). This discrepancy is likely attributable to the critical state of the neonates with AKI. CONCLUSIONS: This is the largest prospective, multicentre study specifically looking at neonatal AKI and need for dialysis in neonates. AKI was seen in 30.7% of neonates (with the need for acute PD in 9% of the AKI group). The odds of needing acute PD were significantly higher among those with significant cardiac disease, inotropes usage, severe peripartum event, requirement of respiratory support in NICU, necrotising enterocolitis, any grade of intraventricular haemorrhage, evidence of fluid overload more than 10% during the first 12 h in NICU and requirement of resuscitation in the delivery room. AKI neonates with PD as compared to AKI neonates without PD had a significantly higher mortality. There is a need to keep a vigilant watch in neonates with risk factors for the development of AKI and need for PD.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Neonatal acute kidney injury risk stratification score: STARZ study.

BACKGROUND: Neonates admitted in the neonatal intensive care unit are vulnerable to acute kidney injury leading to worse outcomes. It is important to identify "at-risk" neonates for early preventive measures. METHODS: The study was a multicenter, national, prospective cohort study done in 11 centers in India. A multivariable logistic regression technique with step-wise backward elimination method was used, and a "Risk Prediction Scoring" was devised [the STARZ score]. RESULTS: The neonates with admission in the NICU within <25.5 h of birth, requirement of positive pressure ventilation in the delivery room, <28 weeks gestational age, sepsis, significant cardiac disease, urine output <1.32 ml/kg/h or serum creatinine ≥0.98 mg/dl during the first 12 h post admission, use of nephrotoxic drugs, use of furosemide, or use of inotrope had a significantly higher risk of AKI at 7 days post admission in the multivariate logistic regression model. This scoring model had a sensitivity of 92.8%, specificity of 87.4% positive predictive value of 80.5%, negative predictive value of 95.6%, and accuracy of 89.4%. CONCLUSIONS: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. IMPACT: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. These neonates with a higher risk stratification score need intense monitoring and daily kidney function assessment. With this intensification of research in the field of AKI risk stratification prediction, there is hope that we will be able to decrease morbidity and mortality associated with AKI in this population.

Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry].

Background: Acute kidney injury (AKI) is a significant problem in neonates, but the evidence is sparse. Neonatal AKI is an independent risk factor for increased mortality and prolonged hospital stay. There are stark differences in the epidemiology of AKI in neonates amongst the developing and the developed world. Increased prevalence of neonatal sepsis, lack of awareness about neonatal AKI and poor access to pediatric nephrologists add to the improper management of neonatal AKI in the developing countries. Methods: This study is a multicentric, national, prospective cohort study [The Indian iconic Neonatal Kidney Educational Registry (TINKER)] conducted in level 2-3 NICUs in 11 centers across India. We have enrolled nearly 2,000 neonates over the study period. Neonates (≤ 28 days) who were admitted in NICU and those who received intravenous (IV) fluids for at least 48 h for hydration and/or nutrition have been included. Data collection included: (1) baseline demographics (2) daily physiologic and laboratory parameters (3) discharge data. KDIGO workgroup AKI definition modified for neonates was used for defining AKI. Data entry was carried out by individual participating centers using a web-based database (akiregistry.org). De-identified data has been maintained and handled by the principal investigator (PI). This collaboration plans to disseminate data through peer-reviewed publications and through presentations at educational conferences. Conclusions: The purpose of this study is to create the first prospective neonatal all-cause AKI data repository and describe the incidence of neonatal AKI in NICUs in the country and determine the risk factors as well as the outcomes of such neonates-both short-term and long-term outcomes. This will eventually spur therapeutic advancements, facilitate decipherment of epidemiological trends, risk factors as well as outcomes and identify disparities in management across the nation.

Long-Term Renal Outcomes in Children With Acute Kidney Injury Post Cardiac Surgery.

INTRODUCTION: The long-term renal outcomes of survivors of pediatric acute kidney injury (AKI) are varied within the current literature, and we aim to establish long-term renal outcomes for pediatric patients after cardiac surgery. We studied long-term renal outcomes and markers of kidney injury in pediatric patients after congenital cardiac surgery. METHODS: In a prospective case-control observational study (the Renal Outcomes in Children with acute Kidney injury post cardiac Surgery [ROCKS] trial) we reviewed all children who underwent cardiac surgery on cardiopulmonary bypass (December 2010-2017). RESULTS: During the study period, 2035 patients underwent cardiac surgery, of whom 9.8% developed AKI postoperatively. Forty-four patients who had postoperative AKI had a long-term follow-up, met our inclusion criteria, and were compared with 49 control subjects. We conducted a univariate analysis of reported parameters. At a median follow-up of 41 months, the cases had significantly higher urine levels of neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1). The biomarkers remained higher after adjusting for the urine creatinine, and the ratio of urine KIM-1/urine creatinine was significantly higher among cases. None of the patients had proteinuria or hypertension on follow-up. The presence of AKI, AKI stage, and younger age were not associated with the occurrence of low glomerular filtration rate (GFR) at follow-up. CONCLUSIONS: Urinary biomarker abnormalities persist years after a congenital cardiac surgery in children, who may have a low GFR on follow-up. The presence of AKI, AKI stage, and younger age at surgery are not associated with the occurrence of low GFR at follow-up. Children with a higher surgical complexity score have lower GFR on follow-up.