The effect of dehydration, hyperchloremia and volume of fluid resuscitation on acute kidney injury in children admitted to hospital with diabetic ketoacidosis.

BACKGROUND: Acute kidney injury (AKI) is a recognized comorbidity in pediatric diabetic ketoacidosis (DKA), although the exact etiology is unclear. The unique physiology of DKA makes dehydration assessments challenging, and these patients potentially receive excessive amounts of intravenous fluids (IVF). We hypothesized that dehydration is over-estimated in pediatric DKA, leading to over-administration of IVF and hyperchloremia that worsens AKI. METHODS: Retrospective cohort of all DKA inpatients at a tertiary pediatric hospital from 2014 to 2019. A total of 145 children were included; reasons for exclusion were pre-existing kidney disease or incomplete medical records. AKI was determined by change in creatinine during admission, and comparison to a calculated baseline value. Linear regression multivariable analysis was used to identify factors associated with AKI. True dehydration was calculated from patients' change in weight, as previously validated. Fluid over-resuscitation was defined as total fluids given above the true dehydration. RESULTS: A total of 19% of patients met KDIGO serum creatinine criteria for AKI on admission. Only 2% had AKI on hospital discharge. True dehydration and high serum urea levels were associated with high serum creatinine levels on admission (p = 0.042; p < 0.001, respectively). Fluid over-resuscitation and hyperchloremia were associated with delayed kidney recovery (p < 0.001). Severity of initial AKI was associated with cerebral edema (p = 0.018). CONCLUSIONS: Dehydration was associated with initial AKI in children with DKA. Persistent AKI and delay to recovery was associated with hyperchloremia and over-resuscitation with IVF, potentially modifiable clinical variables for earlier AKI recovery and reduction in long-term morbidity. This highlights the need to re-address fluid protocols in pediatric DKA.

Paediatric Dialysis at a Tertiary Hospital in South-West Nigeria: A 4-Year Report.

INTRODUCTION: Dialysis is potentially lifesaving in children with acute kidney injury (AKI) or chronic kidney disease (CKD), but availability is limited in low-income countries and lower-middle-income countries (LMICs). METHODS: In the present study, we perform a 4-year study of patients who received peritoneal dialysis (PD) or haemodialysis (HD) at the Paediatric Nephrology Unit of the University College Hospital Ibadan, Nigeria. Subgroup analysis was performed on patients with sepsis or malaria AKI who underwent HD or PD for predictors of in-hospital mortality. RESULTS: A total of 167 children aged 7 days to 18 years, median 7 (interquartile range 3-12) years, (60.5% males) were studied. In total, 129 (77.2%) had AKI, while 38 had CKD. Regarding AKI, 83 children (64.3%) received HD only, 42 underwent PD only, while 4 underwent both HD and PD. Malaria AKI was treated with HD in 43 (51.8%) or PD in 8 (10.5%), while sepsis AKI was treated with HD in 20 (21.4%) or PD in 33 (78.6%). Mortality in AKI was 16.3% overall, 10.8% in children on HD only, and 26.2% in children on PD only. Patients with sepsis AKI had higher mortality compared to patients with malaria AKI (RR 7.96 [1.70-37.37]). Subgroup analysis showed that age, diagnosis, and dialysis modality were not independent risk factors for mortality. The aetiology of CKD was glomerulonephritis in 26 (68.4%): treatment was HD in 36 and PD in 2 with mortality being 26.3%. CONCLUSIONS: PD for AKI showed relatively good outcomes in a LMIC. However, funding and support for a formal dialysis program for the management of AKI and CKD are needed.

Substantial practice variation exists in the management of childhood nephrotic syndrome.

BACKGROUND: Practice variation is common for nephrotic syndrome (NS) treatment. METHODS: A cross-sectional, web-based survey on NS treatment was administered to 58 Canadian pediatric nephrologists with the aim to document existing practice variation and compare practice with the recommendations of the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for NS. RESULTS: Of the 58 nephrologists asked to participate in the survey, 40 (69 %) responded. Among these, 62 % prescribed initial daily glucocorticoid (GC) therapy for 6 weeks, 26 % for 4 weeks by 26 %, and 10 % prescribed 'other'. Alternate-day GC was continued for 6 weeks by 63 % of respondents and for >6 and <6 weeks by 32 and 6 %, respectively. For biopsy-confirmed minimal change disease, 65 and 46 % of respondents chose oral cyclophosphamide for frequently relapsing and steroid-dependent phenotypes, respectively; calcineurin inhibitors or mycophenolate were the second most popular choices. Kidney biopsy was 'always' performed by 16, 39, and 97 % of respondents for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Rituximab had been administered by 60 % of respondents; 22, 56, and 72 % reported that they would consider rituximab for frequently relapsing, steroid-dependent, and steroid-resistant patients, respectively. Most notable differences between practice and Guideline recommendations were first presentation GC duration, GC-sparing agent choices in frequently relapsing and steroid-dependent patients, and biopsy practices. CONCLUSIONS: There is substantial Canadian practice variation in NS treatment. Assessment of factors driving variation and strategies to implement Guideline recommendations are needed.

Cyclooxygenase (COX) Inhibitors and the Newborn Kidney.

This review summarizes our current understanding of the role of cyclo-oxygenase inhibitors (COXI) in influencing the structural development as well as the function of the developing kidney. COXI administered either during pregnancy or after birth can influence kidney development including nephronogenesis, and can decrease renal perfusion and ultrafiltration potentially leading to acute kidney injury in the newborn period. To date, which COX isoform (COX-1 or COX-2) plays a more important role in during fetal development and influences kidney function early in life is not known, though evidence points to a predominant role for COX-2. Clinical implications of the use of COXI in pregnancy and in the newborn infant are also evaluated herein, with specific reference to the potential effects of COXI on nephronogenesis as well as newborn kidney function.

Acute renal replacement therapy in children with diarrhea-associated hemolytic uremic syndrome: a single center 16 years of experience.

Acute kidney injury (AKI) is becoming more prevalent among hospitalized children, its etiologies are shifting, and new treatment modalities are evolving; however, diarrhea-associated hemolytic uremic syndrome (D+HUS) remains the most common primary disease causing AKI in young children. Little has been published about acute renal replacement therapy (ARRT) and its challenges in this population. We describe our single center's experience managing 134 pediatric patients with D+HUS out of whom 58 (43%) required ARRT over the past 16 years. In our cohort, all but one patient were started on peritoneal dialysis (PD). Most patients, 47 (81%), received acute PD on a pediatric inpatient ward. The most common recorded complications in our cohort were peritoneal fluid leaks 13 (22%), peritonitis 11 (20%), and catheter malfunction 5 (9%). Nine patients (16%) needed surgical revision of their PD catheters. There were no bleeding events related to PD despite a mean platelets count of 40.9 (±23.5) × 10(3)/mm(3) and rare use of platelets infusions. Despite its methodological limitations, this paper adds to the limited body of evidence supporting the use of acute PD as the primary ARRT modality in children with D+HUS.

Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A long-term single-centre experience.

BACKGROUND: Reports of long-term incidence trends of endemic diarrhea-associated hemolytic uremic syndrome (D+HUS) are few and inconclusive. OBJECTIVE: To define and analyze the incidence and outcomes of D+HUS over a period of approximately 25 years in a highly endemic region of southern Alberta. METHODS: Annual incidence rates of confirmed cases of D+HUS were compared between two 12-year periods (1980 to 1992 and 1994 to 2006). Differences in therapies used, and some short- and long-term complications observed were also compared between the two periods. RESULTS: The absolute yearly number of D+HUS cases was highly variable. The comparison between the 1980 to 1992, and 1994 to 2006 periods demonstrated a modest 8.8% decrease in the total number of cases. The population-based average annual incidence rates were not significantly different between the two time periods (3.33 cases versus 2.58 cases per 100,000 population per year, respectively; P=0.30). Only supportive care measures were used in the latter period. A mortality rate of lower than 1% in the latter period was one of the lowest ever reported for a large cohort of D+HUS patients. CONCLUSION: The present long-term retrospective study of D+HUS in a highly endemic area documented a modest decrease in the absolute number of cases but no difference in the average annual incidence over an extended period of time.

Hospital-acquired acute hyponatremia and reports of pediatric deaths.

Information from four voluntary reports of hospital-acquired acute hyponatremia leading to the death of otherwise healthy children is highlighted. In this column, we present two cases and information from a recent ISMP Canada Safety Bulletin, as well as two cases reported to ISMP United States. Information is shared to enhance health care practitioners' awareness of the potential for acute hyponatremia and to provide an overview of some of the potential underlying factors.

Outcomes of kidney transplantation in children with nephronophthisis: an analysis of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) Registry.

NPHP is an autosomal recessive chronic tubulointerstitial nephropathy that progresses to ESRD. In the 2006 NAPRTCS report, NPHP was the primary diagnosis in 2.8% of all renal transplant patients. At our pediatric center, that covers a population in which the NPHP1 gene is prevalent, 24% of transplant recipients had a primary diagnosis of NPHP. Since no previous literature reports have documented kidney transplant outcomes in patients with NPHP, a review of the 2006 NAPRTCS database was performed. The results of this review illustrate that patients with NPHP as their underlying kidney disease have a significantly better overall graft survival when compared with all other patients registered in the NAPRTCS database. Sub-analysis demonstrated that this benefit is statistically significant only for LD kidney transplant recipients. CrCl was better in NPHP at all time points from transplant up to five-yr follow-up. Moreover, in NPHP LD transplant recipients the decline of CrCl over five yr was slower compared with non-NPHP LD transplant recipients. Rates of thrombosis, acute, and chronic rejection as well as causes of graft failure were similar in NPHP patients and all other patients. This review demonstrates that NPHP transplant recipients have excellent outcomes that are shown to be better compared with the general pediatric transplant population.

Persistent post-transplant polyuria managed by bilateral native-kidney laparoscopic nephrectomy.

Polyuria is not considered an absolute indication for pre-transplant nephrectomy; however, it may complicate post-transplantation fluid management. Bilateral native-kidney laparoscopic nephrectomy was performed at our centre in two patients (four kidneys) 1 month after they had received a living related-donor renal transplant. The indication for nephrectomy was severe post-transplant polyuria secondary to the patient's underlying disease: juvenile nephronophthisis. Both patients had a persistent post-transplant daily urine output of 7-8 l/day and continued to have a variable serum creatinine level, dependent on intravenous hydration, more then 3 weeks after transplantation. Bilateral laparoscopic native-kidney nephrectomy in children has previously been reported. However, to the best of our knowledge, laparoscopic nephrectomy has not been described after kidney transplantation and certainly not in the immediate post-transplantation period. The procedure was well tolerated and did not affect renal graft function. In fact, following the procedure, serum creatinine levels stabilized, while daily fluid requirements decreased to 2.5-3.5 l/day in both patients. We concluded that bilateral native-kidney nephrectomy can be safely performed in paediatric renal transplant recipients in the immediate post-transplantation period. This new approach may allow preemptive transplantation and avoid the need for a transition period on dialysis in patients for whom pre-transplant nephrectomy is not absolutely indicated.

Invasive Streptococcus pneumoniae infection causing hemolytic uremic syndrome in children: Two recent cases.

INTRODUCTION: Streptococcus pneumoniae is an uncommon cause of hemolytic uremic syndrome (HUS) with a unique pathophysiology that differs from Shiga toxin-related HUS. METHODS: Case descriptions for each patient are provided. Each strain of S pneumoniae was subjected to a pulsed-field gel electrophoresis (PFGE) analysis, Shiga toxin assay and polymerase chain reaction to detect Shiga toxin genes. A review of the current literature was conducted. CASE PRESENTATIONS: Two patients with S pneumoniae-related HUS that presented to the Alberta Children's Hospital, Calgary, Alberta, within four weeks of each other in 2001 are described. Both presented with pneumonia and empyema with associated HUS. Both patients required dialysis, one patient for 10 days and the other for 18 days. Neither patient demonstrated evidence of Shiga toxin-related disease. S pneumoniae isolated from blood or pleural fluid was penicillin susceptible. One isolate was serotype 3 and the other was serotype 14. The two strains had different PFGE patterns. Both patients recovered well with no persistent renal dysfunction. CONCLUSIONS: S pneumoniaecontinues to be an uncommon but important cause of HUS. Most cases can be confirmed or at least considered probable without performing a renal biopsy.