Case Report: Novel compound heterozygous TPRKB variants cause Galloway-Mowat syndrome.

Background: Galloway-Mowat syndrome (GAMOS) is a rare genetic disease characterized by early-onset nephrotic syndrome and microcephaly with central nervous system abnormalities. Pathogenic variants in genes encoding kinase, endopeptidase, and other proteins of small size (KEOPS) complex subunits cause GAMOS. The subunit TPRKB (TP53RK binding protein) has been reported in only two patients with GAMOS with homozygous missense variants. Clinical report: Herein, we described a three-year-old male with GAMOS. He exhibited developmental delay, developmental regression, microcephaly, distinctive facial features, skeletal abnormalities, and epilepsy. Brain magnetic resonance imaging revealed progressive brain atrophy, delayed myelination, T2-hypointense signals in the thalamus, and multiple intracranial abnormal signals on diffusion-weighted imaging. He presented with relapsing nephrotic proteinuria exacerbated by upper respiratory tract infections and progressive renal function decline. Exome sequencing identified compound heterozygous missense and frameshift variants in TPRKB: c.224dup, p.(Ser76IlefsTer3) and c.247C>T, p.(Leu83Phe). Conclusions: Our study supports that pathogenic TPRKB variants cause KEOPS complex-related GAMOS.

Mortality outcomes and clinical background of children on maintenance dialysis without receiving kidney transplantation.

BACKGROUND: Some pediatric patients on maintenance dialysis may need end-of-life care in the future because of being excluded from the indication of kidney transplantation and experiencing difficulty in continuation of their dialysis. This study aimed to thoroughly elucidate mortality outcomes of children on maintenance dialysis including the cause of death and clinical background of exclusion from indication of transplantation. PATIENTS AND METHODS: This single-center retrospective study enrolled 53 children who received kidney transplantation (5) or maintenance peritoneal dialysis (PD, 48) as initial renal replacement therapy (RRT). We examined the selected RRT modalities, mortality outcomes, clinical backgrounds of cause of death, and risk factors of excluding from future the indication of transplantation. RESULTS: Nine (17%) of all 53 patients, all receiving PD (9/48, 19%), were finally excluded from next RRT indication-7 were excluded due to severe extrarenal complications that indicated high risk for transplantation and 2 were excluded due to severe psychomotor retardation and at the guardians' discretion. Patients who were excluded from the indication had a younger age at PD induction and higher proportion of cerebral and cardiac complications or psychomotor retardation than patients who were included in the indication. Of the nine patients, seven died; of which, one patient died due to fatal progression of extrarenal complications and six died due to infectious or noninfectious dialysis-related complications. CONCLUSION: Patients with severe extrarenal complications or psychomotor retardation tend to be excluded from the indication of transplantation. Their condition becomes fatal because of the complications of long-term dialysis and progression in extrarenal complications.

Serum albumin level is associated with mycophenolic acid concentration in children with idiopathic nephrotic syndrome.

Mycophenolate mofetil is effective for the treatment of pediatric idiopathic nephrotic syndrome (INS). The dosage of mycophenolate mofetil is adjusted according to the serum concentration of mycophenolic acid (MPA). Kidney function or cyclosporine (CsA) concentrations affect serum MPA levels. However, few studies have focused on the association between serum concentrations of MPA and albumin. This retrospective observational study aimed to evaluate the relationship between the serum concentrations of MPA and albumin in INS children. Subjects were children with INS who underwent the therapeutic drug monitoring of CsA and MPA. We obtained the serum albumin (sAlb) concentration, estimated glomerular filtration rate (eGFR), age, and MPA and CsA areas under concentration-time curves from 0 to 12 h (AUC0-12). Multiple linear regression analysis and generalized estimating equations were performed to predict values for MPA AUC0-12. We obtained information for 51 INS children with 261 MPA AUC0-12 measurements. The standardized regression coefficients of sAlb, eGFR, CsA AUC0-12, and age were 0.54, - 0.21, - 0.07, and 0.04, respectively. Furthermore, MPA AUC0-12 levels positively correlated with sAlb concentrations (p < 0.001) and were inversely correlated with eGFR values (p = 0.005) but not with CsA AUC0-12 (p = 0.24) and age (p = 0.65).Conclusion: Serum albumin concentration was strongly associated with total MPA concentration compared with kidney function or CsA values. Although patients with INS may have a low serum concentration of total MPA in the presence of low sAlb concentration, close attention should be paid to the interpretation of the low MPA values. What is Known: • The dosage of mycophenolate mofetil is adjusted according to the serum concentration of total mycophenolic acid. • Kidney function, cyclosporin concentrations, or serum albumin concentrations influence serum mycophenolic acid levels. What is New: • Serum albumin concentration is more strongly associated with total mycophenolic acid concentration than kidney function or cyclosporin values. • In children with nephrotic syndrome, the total mycophenolic acid concentration may not increase in the presence of severe hypoalbuminemia.

Transient renal dysfunction with reversible splenial lesion.

We report the case of a 6-month-old boy with transient renal dysfunction who had an intensified signal in the splenium of the corpus callosum on magnetic resonance imaging. He presented to hospital with fever and sudden disturbance of consciousness. Cerebrospinal fluid analysis did not show pleocytosis. The mild consciousness disturbance disappeared after 30 min, but the splenial signal persisted even after 8 days. Further, renal glucosuria, increased excretion of select amino acids, and abnormal fractional excretion of electrolytes were observed, indicating renal tubular dysfunction. The abnormal urinary findings spontaneously resolved by day 9 of hospitalization. The splenial lesion took 21 days to normalize. There were no signs of neurological complications 2 months later. This case suggests the possibility of renal involvement in splenial lesions.