Nonosmotic secretion of arginine vasopressin and salt loss in hyponatremia in Kawasaki disease.

BACKGROUND: The precise mechanism of hyponatremia in Kawasaki disease (KD) remains elusive because assessment of volume status based on serial changes in body weight is lacking in previous reports. METHODS: Seventeen patients who were diagnosed with KD and hyponatremia (serum sodium levels <135 mmol/L) were analyzed. Volume status was assessed based on serial changes in body weight. Plasma arginine vasopressin (ADH), urine electrolytes, and serum cytokine levels were measured on diagnosis of hyponatremia. An increase in body weight by >3% was defined as hypervolemia and a decrease in body weight by >3% was defined as hypovolemia. RESULTS: The volume status was hypervolemic in three patients (18%), euvolemic in 14 (82%), and hypovolemic in none (0%). Five (29%) patients were diagnosed with "syndrome of inappropriate secretion of antidiuretic hormone" (SIADH) and no patients were diagnosed with hypotonic dehydration. The contribution of decreased total exchangeable cations (salt loss) to hyponatremia (5.9% [interquartile range, 4.3%, 6.7%]) was significantly larger than that of increased total body water (-0.7% [-1.8%, 3.1%]) (P = 0.004). Serum interleukin-6 levels were elevated in all of the nine patients who were evaluated. Among the 12 (71%) patients who did not meet the criteria of SIADH and hypotonic dehydration, plasma ADH levels were inappropriately high in ten patients. These patients were also characterized by euvolemic or hypervolemic hyponatremia and salt loss, which might be compatible with a diagnosis of SIADH. CONCLUSIONS: Our study shows that hyponatremia in KD is euvolemic or hypervolemic and is associated with nonosmotic secretion of ADH and salt loss in the majority of patients.

Temple syndrome in a patient with variably methylated CpGs at the primary MEG3/DLK1:IG-DMR and severely hypomethylated CpGs at the secondary MEG3:TSS-DMR.

BACKGROUND: The human chromosome 14q32.2 imprinted region harbors the primary MEG3/DLK1:IG-differentially methylated region (DMR) and secondary MEG3:TSS-DMR. The MEG3:TSS-DMR can remain unmethylated only in the presence of unmethylated MEG3/DLK1:IG-DMR in somatic tissues, but not in the placenta, because of a hierarchical regulation of the methylation pattern between the two DMRs. METHODS: We performed molecular studies in a 4-year-old Japanese girl with Temple syndrome (TS14). RESULTS: Pyrosequencing analysis showed extremely low methylation levels of five CpGs at the MEG3:TSS-DMR and grossly normal methylation levels of four CpGs at the MEG3/DLK1:IG-DMR in leukocytes. HumanMethylation450 BeadChip confirmed marked hypomethylation of the MEG3:TSS-DMR and revealed multilocus imprinting disturbance (MLID) including mild hypomethylation of the H19/IGF2:IG-DMR and mild hypermethylation of the GNAS A/B:TSS-DMR in leukocytes. Bisulfite sequencing showed markedly hypomethylated CpGs at the MEG3:TSS-DMR and irregularly and non-differentially methylated CpGs at the MEG3/DLK1:IG-DMR in leukocytes and apparently normal methylation patterns of the two DMRs in the placenta. Maternal uniparental disomy 14 and a deletion involving this imprinted region were excluded. CONCLUSIONS: Such a methylation pattern of the MEG3/DLK1:IG-DMR has not been reported in patients with TS14. It may be possible that a certain degree of irregular hypomethylation at the MEG3/DLK1:IG-DMR has prevented methylation of the MEG3:TSS-DMR in somatic tissues and that a hypermethylation type MLID has occurred at the MEG3/DLK1:IG-DMR to yield the apparently normal methylation pattern in the placenta.

Morphological and functional analyses of two infants with obstructive renal dysplasia.

Renal dysplasia associated with urinary tract obstruction comprises two distinct phenotypes, i.e., multicystic dysplastic kidney (MCDK) and obstructive renal dysplasia (ORD). MCDK is a common manifestation in infants with renal dysplasia, which is characterized by multiloculated thin-walled cysts with no functional parenchyma and an atretic ureter owing to pyelocalyceal occlusion early in fetal life. In contrast, ORD is an extremely rare condition which is caused by severe obstruction of the distal ureter or urethra. Here, we report two infants with ORD. Both patients manifested unilateral kidney enlargement with multiple cortical cysts, mild hydronephrosis, and marked dilatation of the ipsilateral ureter. Contralateral kidneys and urinary tracts revealed no apparent radiological abnormalities. Serial ultrasonographic studies of fetal and neonatal kidneys in both cases revealed that ureteral dilatation was evident at gestational week 16 and 27, respectively, and most of the cortical cysts disappeared within 1-3 months after birth. The functions of the affected kidneys were severely impaired but evident at the time of birth. These manifestations were consistent with a diagnosis of ORD, and were distinct from the features of MCDK. Our observation of fetal and infantile kidneys in these two cases provides us with a better understanding of the pathogenesis of ORD.

Ischemic colitis as a complication in a patient with steroid-dependent nephrotic syndrome.

We report the case of a 16-year-old male patient with steroid-dependent nephrotic syndrome who developed ischemic colitis. He was diagnosed as having nephrotic syndrome at 10 years of age and had been administered steroid, cyclosporine A, and mizoribine for 7 years. He presented with severe abdominal pain 5 days after intravenous methylprednisolone pulse therapy; thereafter, massive bloody diarrhea developed. Abdominal ultrasonography and computed tomography revealed a marked thickening of the wall of the transverse colon. Colonoscopy confirmed the diagnosis of ischemic colitis. This is the first report of the development of ischemic colitis in a pediatric patient with nephrotic syndrome.

A familial case of multicystic dysplastic kidney.

A familial case of multicystic dysplastic kidney (MCDK) is described. The proband is a one-year-old boy with left MCDK, and his father was also revealed to have unilateral MCDK. The mother had two abortions; the second pregnancy was terminated because of bilateral MCDK of the fetus (Potter anomaly). The two patients and the aborted male fetus did not have any malformations except for MCDK. Thus in this family MCDK occurs as an isolated phenomenon in three individuals within two generations, presumably as a result of autosomal dominant inheritance.