Nurcan Cengiz

Acute Renal Failure in the Neonatal Period

Acute renal failure (ARF) is a common problem in the neonatal intensive care unit (NICU). In most cases, ARF is associated with a primary condition such as sepsis, metabolic diseases, perinatal asphyxia and/or prematurity. This retrospective study investigated the course of illness, therapeutic interventions, early prognosis and risk factors associated with development of ARF in the neonatal period. A total of 1311 neonates were treated in our NICU during the 42‐month study period, and 45 of these babies had ARF. This condition was defined as serum creatinine level above 1.5 mg/dL despite normal maternal renal function. The data collected for each ARF case were contributing condition, cause and clinical course of ARF, gestational age and birth weight, age at the time of diagnosis, treatment, presence of perinatal risk factors and need for mechanical ventilation. The frequency of ARF in the NICU during the study period was 3.4%. Premature newborns constituted 31.1% of the cases. The mean birth weight in the group was 2863 ± 1082 g, and the mean age at diagnosis was 6.2 ± 7.4 days. The causes of ARF were categorized as prerenal in 29 patients (64.4%), renal in 14 patients (31.1%) and postrenal in 2 patients (4.4%). Forty‐seven percent of the cases were nonoliguric ARF. Asphyxia was the most common condition that contributed to ARF (40.0%), followed by sepsis/metabolic disease (22.2%) and feeding problems (17.8%). Therapeutic interventions were supportive in 77.8% of the cases, and dialysis was required in the other 22.2%. The mortality rate in the 45 ARF cases was 24.4%. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were associated with significantly increased mortality (p < 0.05). There were no statistical correlations between mortality rate and perinatal risk factors, oliguria, prematurity or blood urea nitrogen and creatinine levels. The study showed that, at our institution, ARF in the neonatal period is frequently associated with preventable conditions, specifically asphyxia, sepsis and feeding problems. Supportive therapy is effective in most cases of neonatal ARF. Acute renal failure of renal origin, need for dialysis, and need for mechanical ventilation were identified as indicators of poor prognosis in these infants. Early recognition of risk factors and rapid effective treatment of contributing conditions will reduce mortality in neonatal ARF.

Ambulatory blood pressure monitoring and renal functions in children with a solitary kidney.

The aim of this study is to investigate the blood pressure (BP) profile, microalbuminuria, renal functions, and relations with remaining normal kidney size in children with unilateral functioning solitary kidney (UFSK). Sixty-six children with UFSK were equally divided into three groups: unilateral renal agenesis (URA), unilateral atrophic kidney (UAK), and unilateral nephrectomy (UNP). Twenty-two age-, weight-, and height-matched healthy children were considered as a control group. The serum creatinine level and first-morning urine microalbumin and creatinine concentrations were determined by the standard methods. Also, the BP profile was determined by ambulatory blood pressure monitoring (ABPM). We found that the serum creatinine level was higher and creatinine clearance was lower in each patient groups compared to those of the control group (p < 0.05). Compared with the controls, each group of patients had mean office, 24-h, daytime, and night-time systolic and diastolic BP values similar to those of the controls (p > 0.05). An inverse correlation was found between the renal size standard deviation scores (SDS) of normal kidneys and 24-h systolic and diastolic BP load SDS in all of the patients (p < 0.05; r = −0.372, r = −0.295, respectively). The observed relationship between renal size SDS and 24-h mean arterial pressure (MAP), systolic and diastolic BP load SDS suggests that children with UFSK should be evaluated by using ABPM for the risk of hypertension.

Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering, and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis and allows identification of novel candidate genes.

Carotid intima media thickness and left ventricular changes in children with end-stage renal disease

CARDIOVASCULAR disease is one of the most frequent causes of death in adults and children with end-stage renal disease (ERSD). Left ventricular (LV) hypertrophy, arterial wall hypertrophy, and carotid artery luminal enlargement are the most common cardiovascular changes in ESRD patients. Alterations in the arterial vessel walls occur during a presumably long subclinical lag phase of endothelial damage in which there is diffuse thickening of the intima. LV hypertrophy results from decreased LV wall stress and increased systemic vascular resistance. In this study, we evaluated the relationship between early structural changes in the carotid arteries and LV in children with ESRD.

Posterior leukoencephalopathy syndrome in children and adolescents.

Posterior leukoencephalopathy syndrome is a recently identified clinical and radiologic entity. The characteristic radiologic findings are bilateral gray and white matter edema in the posterior regions of the cerebral hemispheres. This article reports clinical and radiologic findings in 10 consecutive episodes of posterior leukoencephalopathy syndrome that were diagnosed in 9 children and adolescents. The causes were immunosuppressive therapy in 7 patients and a combination of renal failure and hypertension in 3. The most common presenting symptoms were seizure and altered consciousness; others included headache, sixth nerve palsy, and cortical blindness. Imaging demonstrated abnormalities in the parietal and occipital lobes in all 10 episodes. The signs and symptoms resolved after immunosuppressive agents were reduced or discontinued, or after uremia and hypertension were corrected. Four patients underwent follow-up cranial imaging, and the images showed nearly complete or complete resolution. The syndrome was clinically reversible in all patients.

Cytomegalovirus infection in a patient with atypical Kawasaki disease

Kawasaki disease (KD) is an acute, febrile, and multisystem vasculitis of early childhood with a striking predilection for the coronary arteries. The most significant complication is coronary artery abnormalities, including coronary aneurysms. The etiology of KD remains unknown. Many infectious agents including viruses have been postulated as possible causes of KD. But standard microbiologic techniques, molecular methods and serologic investigations have failed to identify an etiologic agent. We described a patient with atypical KD during cytomegalovirus infection.

Assessment of left ventricular diastolic function by Doppler tissue imaging in children with end-stage renal disease

AIM To evaluate left ventricular (LV) diastolic function in children with end-stage renal disease (ESRD) using conventional pulsed-Doppler echocardiography and Doppler tissue imaging (DTI), and to compare the findings with these two modalities. METHODS Twenty-four children with ESRD and 22 healthy age- and sex-matched control subjects were assessed with conventional Doppler echocardiography and DTI. The scans of the renal disease patients were done after a dialysis session. Parameters related to LV systolic and diastolic function were compared in the ESRD and control groups. RESULTS The ESRD patients had lower mean mitral E/A ratio both according to conventional Doppler echocardiography and TDI than the control subjects. The ESRD group also had significantly longer isovolumetric relaxation time (116+/-31 ms vs 97+/-3.1 ms, respectively; p<0.001), and significantly longer deceleration time (235+/-44 ms vs 202+/-35 ms, respectively; p<0.01) than the control group. CONCLUSION DTI findings correlate well with conventional Doppler echocardiography findings. Children with ESRD show, after dialysis, echocardiographic signs of LV diastolic dysfunction.

Endothelial nitric oxide synthase gene intron 4 a/b VNTR polymorphism in children with APSGN

The role of endothelial nitric oxide synthase gene intron 4 a/b (eNOS4a/b) variable number of tandem repeats (VNTR) polymorphism in various renal diseases was investigated. We investigated whether the eNOS4a/b VNTR polymorphism is associated with susceptibility to acute poststreptococcal glomerulonephritis (APSGN) and its clinical features. Endothelial NOS4a/b VNTR polymorphism is determined by the polymerase chain reaction in 60 children with APSGN, and 66 healthy controls. The genotype distribution of eNOS4 does not differ between the patients and the controls (X2=5.1, p=0.079). However, the frequency of eNOS4a (eNOS4a/a and eNOS4a/b) genotype is higher in the patients than in the controls (X2=4.5, p=0.046). In the APSGN group we performed renal biopsy on eight patients because of nephrotic syndrome accompanies acute nephritic syndrome or glomerular filtration rate (GFR) is lower than 50% of normal, and found that to carry a/a and a/b genotypes were a significant risk factor for this type presentation (OR=17.3, 95% CI:1.95-152.67, p=0.03). Mean serum creatinine values are found statistically significantly higher in a/a and a/b genotypes when compared with b/b genotypes (p=0.022). Children carrying the “aa” and “ab” genotype or “a” allele of eNOS4 have a greater tendency to develop and clinical presentation of APSGN.

Changes in osmolal gap and osmolality in children with chronic and end-stage renal failure.

within the reference range in patients with renal failure [6] . However, the role of OG and serum osmolality in this condition was not established very well. The aim of this study is to determine the serum OG and osmolality in children with various stages of CRF and the effect of dialysis modalities on these parameters. We also investigated the possible relationship among the changes of OG and serum osmolality before and after HD in patients with CRF. We studied 101 patients (52 boys and 49 girls), with known CRF. Thirty-six patients (age range 5–16 years) underwent HD (HD patients), 29 patients peritoneal dialysis (PD patients) whose age range was 2–14 years, and 25 of them were on continuous ambulatory PD while 4 were treated by continuous cycling PD; 36 nondialyzed (age range 2–16 years) CRF patients (ND patients) were also included. There was a statistically significant difference in age between the PD and HD groups (p = 0.013). All HD patients were treated by bicarbonate dialysis 3 times weekly with 0.4–0.7 m 2 substituted cellulosic membranes. PD was carried out 4–6 times daily in continuous ambulatory PD patients and for 8–10 h/night in continuous cycling PD patients with 1.36% peritoneal dialysis solutions (Dianeal 1.36%, Baxter-Eczacibasi Healthcare, Istanbul, Turkey). There was no medication by mannitol in any groups. Samples of blood were obtained before and

Acute, Reversible Nonoliguric Renal Failure in Two Children Associated With Analgesic-Antipyretic Drugs

Abstract Analgesic-antipyretic agents and nonsteroidal anti-inflammatory drugs are the most commonly used medications worldwide for the treatment of pain and fever in children. Acute renal failure is commonly seen in adults after treatment with analgesic agents. This complication has rarely been reported in children. Here, we describe 2patients admitted to our hospital with acute nonoliguric renal failure temporally associated with ingestion of analgesic-antipyretic drugs at therapeutic doses. The first case was a 16-year-old adolescent boy, who had taken acetaminophen (APAP) and mefenamic acid for the indication of upper respiratory tract infection with daily doses of 1500 and 500 mg, respectively. His serum urea nitrogen and creatinine values were 16 and 1.6 mg/dL. The second case was a 12-year-old boy, who had taken APAP with a daily dose of 500 mg for abdominal pain. His serum urea nitrogen and creatinine values were 21 and 2.29 mg/dL. Both of them recovered with appropriate hydration within a week. Over-the-counter analgesic-antipyretic agents seem innocent but carry the risk of acute renal failure even at therapeutic doses. We believe that increased caution and awareness of the toxic effects of APAP and nonsteroidal anti-inflammatory drugs are needed. We suggest that clinicians should be careful while using analgesic-antipyretic-anti-inflammatory drugs especially in children with subclinical dehydration.