Factors influencing occurrence of peritonitis in Saudi children on peritoneal dialysis.

BACKGROUND: The peritonitis rate among children treated with peritoneal dialysis (PD) has not been widely reported in Saudi Arabia. The study aim was to estimate the peritonitis rate per patient-year and investigate the factors associated with higher peritonitis rates in a sample of PD children at King Abdullah Specialist Children's Hospital-Riyadh (KASCH-R), Saudi Arabia. METHODS: This retrospective cohort study included 27 PD children treated between September 2007 and December 2017 at KASCH-R. We recorded the children's demographic and clinical data, and the frequency of peritonitis. RESULTS: The 27 PD children reviewed (63% girls; mean age = 7.32 years old; range, 1-14 years), resulted in 86 peritonitis diagnoses in which the overall recurrence rate (in at least one episode) was 58/86 (67.4%) with a 95% confidence interval (CI), 56.5 to 77.2%. The rate of peritonitis episodes per patient-year was 0.76 (1 episode per 1.31 patient-year). The generalized Poisson model identified older children (age >  10 years) (adjusted rate ratios [aRR] = 7.273, 95% CI: 1.562-33.860), congenital nephrosis (aRR = 4.677, 95% CI: 1.443-15.155), height below 3rd percentile (aRR = 4.689, 95% CI: 1.874-11.735), weight below 3rd percentile (aRR = 5.388, 95% CI: 1.678-17.302), low albumin level (aRR = 4.041, 95% CI: 2.053-7.956), two-week duration of antibiotic therapy (aRR = 2.947, 95% CI: 1.163-7.468), which were independently associated with a high peritonitis rate. CONCLUSIONS: This study showed a high peritonitis rate in our center. Older children, congenital nephrosis, height and weight below the 3rd percentile, low albumin level, and long duration of antibiotic therapy were associated with a higher rate of peritonitis. An optimal peritonitis prevention strategy or best-practice guideline is needed to reduce and prevent peritonitis occurrence in our center.

Galloway-Mowat syndrome in Taiwan.

We report on two Chinese female infants with multiple congenital anomalies: microcephaly, apparent porencephaly or encephalomalacia, developmental delay, minor facial anomalies, and contractural arachnodactyly. In the first patient, focal glomerulosclerosis was diagnosed histologically by percutaneous renal biopsy due to proteinuria with hematuria. Congenital hypothyroidism presenting with markedly low T3 and T4 was also noted. She died at age 5 months. The second patient had a very similar condition but less severe brain and kidney malformations. A variant of Galloway-Mowat syndrome is suspected.

Congenital nephrosis as a cause of elevated alpha-fetoprotein.

Two cases of congenital nephrosis were detected through routine maternal serum alpha-fetoprotein (MSAFP) screening of 95,135 patients. No other cases of congenital nephrosis from this group were reported, resulting in an incidence of approximately one in 47,500 in this low-risk population. In both of these cases, similar to other reported cases of congenital nephrosis having MSAFP screening, the protein concentrations were greater than or equal to 10 multiples of the median (MOM). Therefore, in the case of an MSAFP over 10 MOM and a normal ultrasound examination, congenital nephrosis should be included in counseling regarding the possibility of undetected malformations. Furthermore, in the case of a pregnancy with elevated amniotic fluid AFP with negative acetylcholinesterase and normal ultrasound, the possibility of congenital nephrosis should be mentioned, regardless of family history or ancestry. When a pregnancy is terminated because of these biochemical findings, special and immediate attention to the fetal kidneys using electron microscopy is necessary to evaluate properly the possibility of congenital nephrosis.

Gel electrophoresis of amniotic fluid acetylcholinesterase as an aid to the prenatal diagnosis of fetal defects.

The presence of absence of a specific acetylcholinesterase (AChE) band was determined by polyacrylamide gel electrophoresis on 272 second trimester amniotic fluid samples. The AChE band was absent from 176 normal samples, including seven which had been scored as false positives by alphafetoprotein (AFP) assay. It was present in all 30 samples from open neural tube defects, of which four had been scored as false negatives by AFP assay. In remaining 66 pregnancies with abnormal outcome, an AChE band was in general present when AFP was raised and absent when it was normal. However, all six cases of congenital nephrosis had raised AFP and no AChE band, while two of 30 pregnancies ending in spontaneous abortion had an AChE band and normal AFP. These results suggest that AChE electrophoresis is a valuable confirmatory technique for the early prenatal diagnosis of fetal abnormalities.

Growth failure due to uremia and congenital nephrosis: growth enhancement by aggressive nutritional therapy.

The metabolic and nutritional effects of long-term parenteral and enteral nutrition were studied in two infants and one child with severe growth failure due to chronic renal failure (two patients) and congenital nephrosis (one patient). Six periods of treatment were analyzed. Both the parenteral nutrition and continuous enteral nutrition were found efficient in enhancing growth and correcting the metabolic abnormalities of uremia. The beneficial effects of this intensive nutrition were smaller in congenital nephrosis, although growth accelerated. Nitrogen balance studies confirmed effective nutrient utilization. The serum levels of calcium and phosphate were normalized as anabolism was achieved in the uremia. In fact, the rapid development of severe hypophosphatemia in one of the patients proved that the "fatal hyperalimentation syndrome" appears to be a specific threat in parenteral nutrition applied in uremia.

Prenatal diagnosis of congenital nephrosis of the Finnish type (CNF) in the second trimester.

Congenital nephrosis of the Finnish type is an hereditary, autosomal recessive disease which leads to death in early infancy. This is a case report concerning an affected fetus with legal interruption in the 24th week of gestation on the basis of certain sonographic changes in the fetal kidneys and changes in the protein profile in amniotic fluid, which were consistent with nephrotic damage of the kidneys. Light and electron microscopy showed evidence of CNF, i.e. increase of mesangial matrix and cells in glomeruli, dilated tubular segments, and effaced and plumb foot-processes of the glomerular epithelial cells. Antenatal diagnosis of CNF therefore seems feasible in the second trimester of gestation by means of AFP determinations in maternal serum and amniotic fluid as well as by using sonographic criteria and determination of proteins in amniotic fluid.

Rare causes of elevated maternal serum alpha-fetoprotein. A report of three cases.

Three rare conditions--amniotic band disruption sequence, placental chorioangioma and congenital nephrosis--were diagnosed in midtrimester because of elevated maternal serum alpha-fetoprotein. The diagnosis is important for genetic counseling and obstetric follow-up.

Intermittent or daily administration of 1-alpha calcidol for nephrectomised infants on peritoneal dialysis?

Secondary hyperparathyroidism and renal osteodystrophy are major problems in patients with end-stage renal failure and may result in poor growth in children on dialysis. Whether vitamin D sterols should be given intermittently or daily remains a controversial issue. We studied 16 bilaterally nephrectomised infants with congenital nephrosis of the Finnish type (median age 0.54 years), all on peritoneal dialysis. Nine of them were receiving intermittent 1-alpha calcidol therapy and seven daily 1-alpha calcidol therapy. The target serum parathyroid hormone (PTH) level was 2-3 times the upper limit of normal (ULN). There were no statistically significant differences in PTH values between the groups (1.7-times vs 0.5-times the ULN at 3 months and 3.1-times vs 3.4-times the ULN at 6 months, respectively). The required weekly doses of 1-alpha calcidol were low, and there were no significant differences between the intermittent and daily groups (0.06 microg/kg vs 0.04 microg/kg at 3 months and 0.09 microg/kg vs 0.05 microg/kg at 6 months, respectively). The infants on intermittent 1-alpha calcidol showed significant catch-up growth during dialysis after nephrectomy relative to the infants on daily 1-alpha calcidol (-1.6 SD to -0.7 SD vs -1.4 SD to -1.0 SD, respectively; P < 0.05). Our results indicate that either intermittent or daily vitamin D analogue therapy, if started early, will prevent secondary hyperparathyroidism equally well in children on peritoneal dialysis (PD), but intermittent therapy might be more favourable for growth.

Renal pathology of fetal congenital nephrosis.

In 15 fetuses with congenital nephrosis, distinct colloid-filled cystic tubular dilations were seen scattered in the renal cortex. Similar structures were not present in the controls. It is suggested that these structures are pathognomonic of congenital nephrosis in the fetus and make diagnosis possible even without electron microscopy.

Fetal proteinuria in diagnosis of congenital nephrosis detected by raised alpha-fetoprotein in maternal serum.

High concentrations of alpha-fetoprotein (alpha-FP) were found at 14, 19, and 21 weeks gestation in the serum of a woman with a history of unexplained fetal death in her previous pregnancies. The alpha-FP concentration of the liquor also was high at 21 weeks and the pregnancy was terminated. Though the fetus was macroscopically normal, measurement of albumin, alpha-FP, IgG, and alpha2-macroglobulin in the fetal urine showed a selective proteinuria, and congenital nephrosis was diagnosed after examination of the fetal kidneys by electron microscopy. Possibly some fetuses reported to be "false-positive for neural tube defect" may have had renal lesions of this nature. Examination of fetal urine may be the simplest initial diagnostic procedure in any future case.

Pachygyria and congenital nephrosis disorder of migration and neuronal orientation.

A case of pachygyria with associated nephrosis has been studied. Several microscopic abnormalities have been identified: cytoarchitectonic disorders including neuronal ectopies in the molecular layer and in the meninges, improperly oriented neurons shown with Golgi stain, fetal aspect of inferior olives. The mechanism of the disorder of migration and neuronal and dendritic orientation are discussed. The significance of the association of microcephaly and nephrosis is also reviewed in light of recent literature.

Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia.

The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = -0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C-II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C-II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF.

Congenital nephrosis: detection of index cases through maternal serum alpha-fetoprotein screening.

Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid alpha-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum alpha-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum alpha-fetoprotein, with unexplained and marked elevations of amniotic fluid alpha-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin.

Alpha-fetoprotein in antenatal diagnosis of congenital nephrosis.

Alpha-fetoprotein (A.F.P,) levels were found to ge significantly raised in maternal serum and amniotic-fluid samples form the 16th and 18th weeks of gestation in a woman with an apparently normal fetus but with histological evidence of congenital nephrosis of the Finnish type. Increased concentrations of A.F.P. in early pregnancy with a living fetus are therefore not specific for neural-tube defects; More likely they result from the fetal circulation. Extended investigations, including kidney morphology, should be done in cases of apparent false-positive A.F.P. tests.

Antenatal screening for congenital nephrosis in Finland by maternal serum alpha-fetoprotein.

In the Kuopio and North-Karelia districts of Finland 10724 pregnancies were screened for congenital nephrosis by maternal serum alpha-fetoprotein (AFP) measurement. Outcome was known for 10504 (98%) pregnancies, of which 509 (4 X 8%) had a serum AFP level greater than or equal to 2 X 5 multiples of the normal median (MoM) at 15-18 weeks gestation. After exclusion of those women who had a normal serum AFP level (less than 2 X 5 MoM) in a second sample, 'wrong dates' or multiple pregnancy, 267 (2 X 5%) remained with a high serum AFP level. Amniocentesis was carried out in 225 (2 X 1%) and 16 women had an amniotic fluid AFP level greater than 10 SD above the normal mean. In this group there were six fetuses with congenital nephrosis (four confirmed and two suspected), six other serious malformations (including an intrauterine death) and four without obvious abnormality. In the 98% pregnancies followed up there were no infants with congenital nephrosis that had been missed. Babies with congenital nephrosis require permanent hospitalization and have a mean survival of 8 months. In Finland, within certain areas, the birth prevalence is as high as 1 in 2600 per year. In such areas maternal serum AFP measurement appears to be a useful method of screening for congenital nephrosis. The service was also well accepted since 94% of the women with raised serum AFP levels wished to be screened again in a future pregnancy.

Prenatal characteristics of congenital nephrosis: results of a survey.

The purpose of this study was to evaluate the prenatal characteristics of congenital nephrosis of the Finnish type (CNF). Patients presenting with elevated maternal serum and/or amniotic fluid alpha-fetoprotein levels, normal ultrasound examinations and normal fetal karyotypes were included. A retrospective cohort study was conducted using questionnaires sent to all board certified clinical geneticists. Perinatal outcome, including histologic verification of CNF, was obtained. Forty index cases met the above criteria. Ten cases ultimately did not have the diagnosis of CNF, with a median MSAFP level of 7.59 MoM (range 2.7-27.64 MoM) and a median AFAFP level of 10.99 MoM (range 1.47-128.6 MoM). In the affected cohort of index pregnancies, the initial median MSAFP level was 14.49 MoM (range 3.1-38.0 MoM); the median AFAFP level was 40.0 MoM (range 2.4-80.9). MSAFP and AFAFP levels may be lower than previously recognized in patients carrying fetuses with CNF. There is significant overlap between the affected and unaffected patients.

Pregnancy specific beta 1-glycoprotein and human chorionic gonadotrophin levels n amniotic fluid and maternal serum in the first half of pregnancy.

Pregnancy-specific beta 1-glycoprotein (PSBG) and chorionic gonadotrophin (HCG) were measured by radioimmunoassay in the amniotic fluid of 99 normal pregnancies, 19 pregnancies of women at risk of having another child with congenital nephrosis and 8 pregnancies in which the fetus had a neural tube defect. Maternal serum PSBG and HCG levels were estimated in 52 normal pregnancies and 15 pregnancies at risk for congenital nephrosis. Both amniotic fluid and maternal serum PSBG levels increased in either compartment after 14th week of pregnancy. There was a positive correlation between maternal serum and amniotic fluid PSBG concentrations (P less than 0.001), between maternal serum and amniotic fluid HCG concentrations (P less than 0.001), and between the amniotic fluid PSBG and HCG levels (P less than 0.05) at a given week of pregnancy (wk 15). On average the maternal serum PSBG level was 20-50 times and the HCG level 2-3 times the amniotic fluid level of normal pregnancies. In cases with a neural tube defect the amniotic fluid PSBG and HCG values were similar to those in normal pregnancy. In congenital nephrosis the amniotic fluid HCG concentration was higher than normal at 15-16 weeks of gestation (P less than 0.05), whereas the amniotic fluid PSBG concentration was normal. Thus, placental pathology in congenital nephrosis appears to be reflected as an increased amniotic fluid concentration of HCG in the second trimester.