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.

Impact of graft loss among kidney diseases with a high risk of post-transplant recurrence in the paediatric population.

BACKGROUND: Some kidney diseases tend to recur in the renal allograft after transplantation. We studied the risk of graft loss among primary renal diseases known for their high risk of recurrence and compared it with that of patients with hypoplasia and/or dysplasia. METHODS: Within the European Society of Paediatric Nephrology and European Renal Association and European Dialysis and Transplant Association (ESPN/ERA-EDTA) registry, we studied children from 33 countries who received a kidney transplant before the age of 20 between 1990 and 2009. Patients were censored after 5 years of follow-up and cumulative incidence competing risk analysis was used to calculate survival curves. RESULTS: Patients with focal and segmental glomerulosclerosis (FSGS), haemolytic uraemic syndrome (HUS), membranoproliferative glomerulonephritis Type I or II (MPGN), IgA nephropathy or Henoch Schönlein Purpura (HSP/IgA) or systemic lupus erythomatosus (SLE) underwent pre-emptive transplantation significantly less often than patients with hypoplasia and/or dysplasia. The rate of living donation was lower among patients with FSGS and SLE than in patients with hypoplasia and/or dysplasia. In comparison with hypoplasia and/or dysplasia patients with a risk of 14.4%, the 5-year risk of graft loss was significantly increased in patients with FSGS (25.7%) and MPGN (32.4%) while it was not significantly increased in children with HUS (18.9%), HSP/IgA (16.3%) or SLE (20.3%). One-year graft survival strongly improved among HUS patients from 17.1% in 1995-1999 to 3.6% in 2005-2009 and was not accompanied by a decrease in the number of transplantations. CONCLUSION: The risk of graft loss is increased among specific causes of renal failure with a high risk of post-transplant recurrence. It seems likely that, due to anticipation of such risk, physicians perform less pre-emptive transplantation and provide fewer grafts from living related donors in patients with these conditions. Improved risk stratification by physicians, resulting in the identification of patients with HUS at higher or lower risk of recurrence, might explain the much improved graft survival rates.

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.

Recurrent urinary tract infection in girls: do urodynamic, behavioral and functional abnormalities play a role?

BACKGROUND: To determine urodynamic, behavioral and functional abnormalities predisposing to recurrent urinary tract infection in 5- to 17-year-old girls. METHODS: A prospective case-control study was carried out. A total of 148 girls met inclusion criteria. They received a careful evaluation including complete history, voiding-drinking diary, bowel questionnaire, physical investigation, sonography, voiding cystourethrogram and urodynamic investigation. RESULTS: In a multivariate model, independent risk factors for recurrent urinary tract infection included age 20 mL (OR=1.1; 95% CI, 1.0-1.1). CONCLUSIONS: Independent risk factors for recurrent urinary tract infection were age

[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.

[Dysfunction of lower urinary tract in 5-18 years old children with recurrent urinary tract infections]. / Apatiniu slapimo organu funkcijos pokyciai 5-18 metu vaikams, sergantiems pasikartojancia slapimo organu infekcija.

The purpose of this article was to evaluate function of lower urinary tract for 5-18 years old children with recurrent urinary tract infections and to compare urodynamic changes in two groups: with recurrent lower urinary tract infections and with recurrent upper urinary tract infections. 35 urodynamic studies in 5-18 years old children (3 boys and 32 girls) with recurrent urinary tract infection were performed at the Clinic of Children's Diseases of Kaunas University of Medicine in 2004. 21 of these children had recurrent lower urinary tract infections and 14 recurrent upper urinary tract infections. Changes in urodynamics were present in 91.4% of children: in all children with recurrent lower urinary tract infections and in 11 children with upper recurrent urinary tract infections (78.6%). Detrusor instability was found in 20 (57.1%) children: in 14 (66,7%) with recurrent lower urinary tract infections and in 6 (42.9%) with recurrent upper urinary tract infections. In 32 (85%) children detrusor instability was accompanied by changes in bladder volume. Changes of bladder volume were present for 26 (74.3%) children with recurrent urinary tract infections. Detrusor after contraction was diagnosed in 57.1% of children with recurrent lower urinary tract infections and in 28.6% with recurrent upper urinary tract infections. For children with recurrent urinary tract infections attention for urinary tract dysfunction must be paid.

Denys-Drash syndrome.

Constitutional missense mutations in the WT1 gene are usually associated with Denys-Drash syndrome. This rare syndrome is characterized by a rapid progressive nephropathy, male pseudohermaphroditism, and an increased risk for Wilms tumor. We report on a patient with incomplete Denys-Drash syndrome, which was evident by the clinical data and proved by molecular genetics methods. The patient has the mutation p.R394W in the WT1 gene and clinical symptoms of Denys-Drash syndrome.

[Changes of etiology and management of childhood urinary tract infection during the period of 1994-2002 (data of Kaunas University of Medicine Hospital)]. / Vaiku slapimo organu infekcijos etiologiniu faktoriu kitimas ir diagnostikos bei gydymo taktikos pokyciai (Kauno medicinos universiteto kliniku 1994-2002 m. duomenys).

The purpose of this article was to establish changes of age, etiology, diagnostics and treatment for children, who were treated for urinary tract infection in Clinic of Children Diseases, Kaunas University of Medicine Hospital in 1994-1998 and 1999-2002. Seven hundred fifty children urinary tract infections were treated during the period of 1994-1998, and 673--during the period of 1999-2002. Female patients had urinary tract infection nearly five times more than male patients in other age groups. Rate of urinary tract infection in male patients under one year age was greater than in female in this age group (p=0.0001). Greater incidence of urinary tract infection in age group under one year age was established. The incidence among male patients with urinary tract infection grew from 37.8% to 64.0% (p=0.0001) and among female patients--from 9.6% to 18.1% (p<0.0001). More vesicoureteral refluxes (VUR) were diagnosed: 44 (7.8%) in period 1994-1998 and 52 (9.0%) in the period 1999-2002. More than one third of all VUR (36.5%) were diagnosed in age group under one year. The incidence of VUR in this group was greater for male than for female patients (p=0.015). More positive urinary culture for patients with pyelonephritis were in period 1999-2002 (74.6%) than in 1994-1998 (66.8%). The incidence of microorganisms was nearly the same. E. coli was found in 83.4% and in 83.9% of all positive urinary cultures. Sensitivity to the commonly used antibiotics was better (p<0.0001). Pyelonephritis mostly was treated with gentamycin.