Epidemiology of Chronic Kidney Disease in Children: A Report from Lithuania.

Background and Objectives: The data on the prevalence of chronic kidney disease (CKD) in the pediatric population are limited. The prevalence of CKD ranges from 56 to 74.7 cases per million of the age-related population (pmarp). The most common cause of CKD among children is congenital anomalies of the kidney and urinary tract (CAKUT). With progressing CKD, various complications occur, and end-stage renal disease (ESRD) can develop. The aim of the study was to determine the causes, stage, prevalence, and clinical signs of CKD and demand for RRT (renal replacement therapy) among Lithuanian children in 2017 and to compare the epidemiological data of CKD with the data of 1997 and 2006. Materials and Methods: The data of 172 Lithuanian children who had a diagnosis of CKD (stage 2-5) in 1997 (n = 41), in 2006 (n = 65), and in 2017 (n = 66) were retrospectively analyzed. Physical development and clinical signs of children who had CKD (stage 2-5) in 2017 were assessed. Results: The prevalence of CKD stages 2-5 was 48.0 pmarp in 1997; 88.7 in 2006; and 132.1 in 2017 (p < 0.01). Congenital and hereditary diseases of the kidney in 1997 accounted for 66% of all CKD causes; in 2006, for 70%; and in 2017, for 79%. In 2017, children with CKD stages 4 or 5 (except transplanted children) had hypertension (87.5%) and anemia (50%) (p < 0.01). Children under ≤2 years with CKD were at a 3-fold greater risk of having elevated blood pressure (OR = 3.375, 95% CI: 1.186-9.904). Conclusions: There was no change in the number of children with CKD in Lithuania; however, the prevalence of CKD increased due to reduced pediatric population. CAKUT remains the main cause of CKD at all time periods. Among children with CKD stages 4 or 5, there were more children with hypertension and anemia. In children who were diagnosed with CKD at an early age hypertension developed at a younger age.

Early Diagnosis and Prognostic Value of Acute Kidney Injury in Critically Ill Patients.

Background and objectives: In hospitalized children, acute kidney injury (AKI) remains to be a frequent and serious condition, associated with increased patient mortality and morbidity. Identifying early biomarkers of AKI and patient groups at the risk of developing AKI is of crucial importance in current clinical practice. Specific human protein urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin 18 (uIL-18) levels have been reported to peak specifically at the early stages of AKI before a rise in serum creatinine (sCr). Therefore, the aim of our study was to determine changes in uNGAL and uIL-18 levels among critically ill children and to identify the patient groups at the highest risk of developing AKI. Materials and methods: This single-center prospective observational study included 107 critically ill children aged from 1 month to 18 years, who were treated in the Pediatric Intensive Care Unit (PICU) of Lithuanian University of Health Sciences Hospital Kauno Klinikos from 1 December 2013, to 30 November 2016. The patients were divided into two groups: those who did not develop AKI (Group 1) and those who developed AKI (Group 2). Results: A total of 68 (63.6%) boys and 39 (36.4%) girls were enrolled in the study. The mean age of the patients was 101.30 ± 75.90 months. The mean length of stay in PICU and hospital was 7.91 ± 11.07 and 31.29 ± 39.09 days, respectively. A total of 32 (29.9%) children developed AKI. Of them, 29 (90.6%) cases of AKI were documented within the first three days from admission to hospital. In all cases, AKI was caused by diseases of non-renal origin. There was a significant association between the uNGAL level and AKI between Groups 1 and 2 both on day 1 (p = 0.04) and day 3 (p = 0.018). Differences in uNGAL normalized to creatinine in the urine (uCr) (uNGAL/uCr) between the groups on days 1 and 3 were also statistically significant (p = 0.007 and p = 0.015, respectively). uNGAL was found to be a good prognostic marker. No significant associations between uIL-18 or Uil-18/uCr and development of AKI were found. However, the uIL-18 level of >69.24 pg/mL during the first 24 hours was associated with an eightfold greater risk of AKI progression (OR = 8.33, 95% CI = 1.39-49.87, p = 0.023). The AUC for uIL-18 was 73.4% with a sensitivity of 62.59% and a specificity of 83.3%. Age of <20 months, Pediatric Index of Mortality 2 (PIM2) score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of three and more organ systems, PICU length of stay more than three days, and length of mechanical ventilation of >five days were associated with a greater risk of developing AKI. Conclusions: Significant risk factors for AKI were age of <20 months, PIM2 score of >2.5% on admission to the PICU, multiple organ dysfunction syndrome with dysfunction of 3 and more organ systems, PICU length of stay of more than three days, and length of mechanical ventilation of > five days. uNGAL was identified as a good prognostic marker of AKI. On admission to PICU, uNGAL should be measured within the first three days in patients at the risk of developing AKI. The uIL-18 level on the first day was found to be as a biomarker predicting the progression of AKI.

Renal Replacement Therapy in Children in Lithuania: Challenges, Trends, and Outcomes.

Background and Objectives: Pediatric renal replacement therapy (RRT) in Lithuania resumed in 1994 after a 12-year pause in renal transplantation. Management of end stage renal disease (ESRD) has changed, and outcomes have improved over decades. Our aim was to evaluate the dynamics of RRT in Lithuania in the period 1994⁻2015, describe its distinctive features, and compare our results with other countries. Materials and Methods: Data between 1994 and 2015 were collected from patients under the age of 18 years with ESRD receiving RRT. The data included: Hemodialysis (HD), peritoneal dialysis (PD), transplantation incidence and prevalence, transplant waiting time, dialysis modalities before transplantation, causes of ESRD and gender distribution in transplanted patients, and patient and graft survival. Results: RRT incidence and prevalence maintained an increase up until 2009. Sixty-four transplantations were performed. Juvenile nephronophthisis (25.9%) was the primary cause of ESRD in transplanted children. The transplant waiting time median was 8.0 months. The male to female ratio post-transplantation was 1.02. Patient survival after transplantation at 10 years was 90.0%, while graft survival for living (related) was 77.0% and 51.1% for deceased. Twelve patients died while on RRT. Conclusions: RRT numbers are increasing in Lithuania. HD is the primary treatment of choice before transplantation, with continued low numbers of preemptive transplantation. Patient survival post-transplantation is favorable, though graft survival is less satisfactory.

Successful living-related renal transplantation in a patient with factor H antibody-associated atypical hemolytic uremic syndrome.

CFH-Ab-associated aHUS requires different diagnostic and therapeutic approaches and then the genetically defined aHUS forms. The risk of post-transplant recurrence with graft dysfunction in CFH-Ab aHUS is not well documented. It is suggested that recurrence can be expected if a significant CFH-Ab load persists at the time of transplantation. A pretransplant procedure to reduce CFH-Ab titer seems reasonable, but accurate recommendations are lacking. Whether further prophylactic interventions after transplantation are necessary has to be decided on an individual basis. We report the case of a late diagnosed CFH-Ab HUS with initial ESRD and a successful living-related renal transplantation over a post-transplant period of four and a half years on the basis of a prophylactic pretransplant IVIG admission.

Long-term follow-up of children with typical hemolytic uremic syndrome.

OBJECTIVE: The aim of the study was to determine the associations of the acute period course with late-emerging sequelae in children with typical hemolytic uremic syndrome (HUS). MATERIALS AND METHODS: The data of 62 children with typical HUS during the acute phase were retrospectively analyzed by age, sex, duration of anuria/oliguria, method and duration of renal replacement therapy, proteinuria, hypertension, and renal function. The data of 33 children at 10-year follow-up after the onset of the disease were evaluated for changes in hypertension, proteinuria, and renal function. RESULTS: In the acute phase of the disease (n=62), hypertension was documented in 75.8% of the children; proteinuria, in 85.5%; and renal dysfunction, in 100%. At 10 years after the onset of the disease (n=33), hypertension was documented in 12.1%, 6.1%, and 24.2% at 1-, 5-, and ≥10-year follow-ups, respectively, and more often in children aged <1 year at the onset of the disease. Proteinuria was found in 15.2%, 9.1%, and 33.3% of the patients, respectively. After ≥10 years, hypertension developed for the first time in 6.1% of the patients. Renal injury of varying degrees was seen in 15.2% of the children at the 1-year follow-up, and after ≥10 years the proportion increased to 33.3%. CONCLUSIONS: At 10 years after the acute phase of typical HUS in children, the prevalence of hypertension and proteinuria at 1- and 5-year follow-ups decreased, but after 10 years it started to increase. As much as 6.1% of the children developed hypertension or proteinuria for the first time at 10 years. Hypertension was documented more frequently in children who were younger than <1 year at the onset of the disease. Renal dysfunction after 5 and 10 years remained in more than one-third of cases, and it was observed more often if hypertension was documented at the acute period.

Acute kidney injury in pediatric patients: experience of a single center during an 11-year period.

UNLABELLED: The aim of our study was to determine the causes of acute kidney injury (AKI) in children, to compare outcomes between two periods--1998-2003 and 2004-2008--and to evaluate the influence of new methods of renal replacement therapy on mortality. MATERIAL AND METHODS: A retrospective analysis of medical record data of all children treated for AKI at the Clinic of Children Diseases, Hospital of Kaunas University of Medicine, during the period of 1998-2008 was made. Both periods were compared regarding various variables. RESULTS: Of the 179 children with AKI, 75 (41.9%) were treated during 1998-2003 and 104 (58.1%) during 2004-2008. Primary glomerular disease and sepsis were the leading causes of AKI in both the periods. AKI without involvement of other organs was diagnosed for 106 (59.2%) children: for 42 (56.0%) children in the first period and 64 (61.5%) in the second. A total of 124 (69.3%) children were treated in a pediatric intensive care unit. Multiple organ dysfunction syndrome with AKI was diagnosed for 33 (44%) patients in the first period and for 40 (38.5%) in the second. A significant decrease in mortality among patients with multiple organ dysfunction syndrome during the second period was observed (78.8% vs. 37.5%). CONCLUSIONS: More than half of patients had secondary acute kidney injury of nonrenal origin. More than two-thirds (69.3%) of patients with AKI were treated in the pediatric intensive care unit. Multiple organ dysfunction syndrome was diagnosed for 40.8% of children with AKI. Renal replacement therapy was indicated for one-third of patients with AKI. A 2.5-fold decrease in mortality was observed in the second period as compared to the first one.

[Etiology, prevalence of chronic renal failure and growth retardation in Lithuanian children]. / Lietuvos vaiku letinio inkstu nepakankamumo paplitimas, priezastys ir augimo atsilikimas.

The aim of the study was to evaluate the causes, prevalence, and grades of chronic renal failure in Lithuanian children and to assess its influence on children's growth. The study was performed in Vilnius University Children's Hospital and Clinic of Children's Diseases, Kaunas University of Medicine. By March 31, 2006, 65 children with chronic renal failure had been registered. The prevalence was 88.3 cases per million children. The mean age was 10.8+/-4.9 years. The leading causes of chronic renal failure were congenital diseases (37%) and obstruction with interstitial nephritis (33.8%). At presentation, 23 (35.40%) children had mild, 17 (26.15%) had moderate, 9 (23.85%) had severe renal failure, and 16 (24.6%) had end-stage renal disease. Fourteen (21.54%) children were below the third percentile in height for their age. Growth failure was observed in one (4.35%) child with Grade 1 renal failure. The deterioration of renal function had a significant influence on growth impairment, and 13 (30.95%) children with glomerular filtration rate of less than 60 mL/min/1.73 m2 and 7 (43.75%) with end-stage renal disease had a height below the third percentile. Growth retardation as one of the symptoms of impairment of children's physical development depends on the severity of renal function.

[The clinical course and long-term outcome of hemolytic-uremic syndrome in children]. / Vaiku hemolizinio ureminio sindromo klinikine eiga ir velyvosios baigtys.

The aim of this study was to evaluate the long-term outcome of hemolytic-uremic syndrome in children and the dependence of outcome on severity of the acute phase of the illness. We analyzed data of 20 children who were hospitalized and treated at the Clinic of Children's Diseases, Kaunas University of Medicine Hospital, during 1995-2006. Data were obtained from case histories and outpatient case records with the help of prepared questionnaire. The course of acute disease and health status were evaluated at discharge from hospital and at 6-month, 1-year, and 3-year follow-ups. There were 8 boys and 12 girls in the study group; their age ranged from 3 months to 12 years. According to the clinical course of the acute phase of the illness, children were divided into two groups. Group A (severe course) consisted of 15 patients with blood leucocytosis (more than 20x10(9)/L) and signs of CNS involvement, who required renal replacement therapy. Group B (mild course) consisted of five children who did not have such symptoms. Twelve (60%) children underwent dialysis during acute illness; two patients died (10%). One (20%) patient in Group B had proteinuria, four (80%) had renal insufficiency, and three (60%) had arterial hypertension at discharge from hospital. Subsequently these changes disappeared, and 3 years later arterial hypertension was detected in 1 (25%) patient in Group B. Eight (61.5%) patients from Group A had renal insufficiency, nine (69.2%) had proteinuria, and two (15.4 %) had arterial hypertension at discharge from hospital. Three years later from the onset of the disease, two (20%) patients had arterial hypertension, proteinuria was detected in two (20%) patients, and renal insufficiency remained in six (60%) children. Our data revealed that the outcomes of the disease are strongly influenced by the severity of the acute phase of the illness.

[Etiology and outcomes of acute renal failure in childhood]. / Vaiku uminio inkstu nepakankamumo priezastys ir baigtys.

The aim of the research was to determine causes of acute renal failure in children, their outcome and to define risk factors associated with mortality. 75 children with acute renal failure, who were treated at the Clinic of Children's Diseases of Kaunas University of Medicine between 1998-2003 years, were included in the study. The age range of patients was 1 month to 16 years. They were divided into two groups. Acute renal failure was diagnosed in 42 (56%) patients (the first study group) and in 33 (44%) patients acute renal failure was together with multiple organ failure (the second study group). In the first study group 69% of cases of acute renal failure were found to be due to renal diseases and in the second study group 97% were because of extrarenal diseases. Sepsis was the most frequent cause of acute renal failure in the second group (p<0.02). Dialysis was made for 28% patients. Hypertension was diagnosed more often in the first patients group (p<0.05). Hypertension persisted in 9 (36%) patients after recovery. Chronic renal failure developed in two patients. 28 (37.3%) patients of the original study group died. Mortality rate for children with multiple organ failure was higher than for the children, who had renal insufficiency only (78.8% vs 4.8%; p<0.001). Mortality rate of infants in the first study group was higher than for children of the same age in the second group (p<0.001). Mortality rate for children, who had oliguria or anuria, was higher in the second group, too (p<0.001).