RESUMO
Recent studies have described several children with very early-onset polycystic kidney disease (PKD) that mimicked autosomal recessive polycystic kidney disease because of 2 hypomorphic PKD1 gene variants. However, no reports have described pathological changes in the primary cilia in these cases. We analyzed the primary cilia in the kidney tubules of an early elementary school child who had very early-onset PKD and a history of large, echogenic kidneys in utero. There was no family history of autosomal dominant PKD. The patient developed kidney failure and received a living-donor kidney transplant from his father. Genetic analysis revealed compound heterozygous variants in the PKD1 gene: c.3876C>A (p. Phe1292Leu) and c.5957C>T (p. Thr1986Met). These variants were likely pathogenic based on in silico analysis. The absence of kidney cysts in the parents suggested that these variants were hypomorphic alleles. Pathological examination of the patient's excised kidney showed prominent dilatation of the proximal and distal tubules. Immunofluorescence staining for α-tubulin showed pronounced elongation of the primary cilia. These findings suggest that the hypomorphic PKD1 variants expressed in this patient with very early-onset PKD were pathogenic.
RESUMO
MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, progressive kidney failure, and sensorineural hearing loss. We describe a patient with MYH9-RD and a normal platelet count. A 13-year-old boy with a normal platelet count presented with proteinuria and hematuria and underwent a kidney biopsy. Light microscopy showed mild mesangial matrix expansion. Electron microscopy showed thinning of the glomerular basement membrane and splitting of the lamina densa. A tentative diagnosis of Alport syndrome was made. Unexpectedly, genetic analysis revealed a de novo MYH9 gene variant (p.Gln1068_Leu1074dup). A peripheral blood smear examination showed giant platelets and leukocyte inclusion bodies, confirming a diagnosis of MYH9-RD. In summary, we described a patient with MYH9-RD without thrombocytopenia who showed glomerular basement membrane abnormalities similar to Alport syndrome. Peripheral blood smear examinations may be helpful for an appropriate diagnosis of MYH9-RD, even in patients with proteinuria and a normal platelet count.
RESUMO
A transplant of a portion of the bladder with an en bloc kidney from a 2-year-old donor was previously reported in a 12-month-old girl due to her extremely small bladder. Bilateral kidneys were transplanted en bloc with their ureters connected to a patch of the donor bladder (bladder patch technique). The long-term outcomes and complications of this technique have not been documented. Here, we report a long-term, 17-year follow-up of this patient with an evaluation of whole bladder functions at 18 years of age. The patient has had no episodes of urinary tract infections. Cystoscopy showed a viable transplanted bladder with a well-perfused mucosa. We observed that the native bladder has stretched over time, forming more than half of the bladder wall. Urodynamic studies showed preserved bladder compliance at 43 mL/cmH2O, and native bladder contractility was preserved. Prolonged voiding time and postvoid residual urine were also observed. These findings were suggestive of detrusor underactivity. No reï¬ux across the donor ureterovesical junctions was observed. The recipient was instructed to continue timed voiding and double voiding to empty the bladder. In conclusion, en bloc kidney transplantation with a bladder patch is a feasible and safe option for kidney transplant recipients with a small bladder capacity.
RESUMO
BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) frequently recurs after kidney transplantation and is associated with poor graft survival. Patients who do not achieve remission (nonresponders) have an especially poor graft survival. However, the characteristics that may affect graft survival in nonresponders are unknown. This study aimed to determine the clinical characteristics associated with graft survival in nonresponders. METHODS: We retrospectively collected the clinical records of patients with FSGS and an age at onset <16 years who experienced posttransplant recurrence of FSGS at six hospitals in Japan from 1993 to 2018. RESULTS: Eight nonresponders with recurrent FSGS were enrolled in this study. The median time to recurrence after kidney transplantation was 1 day (interquartile range, 1-2 days). All patients received therapeutic plasma exchange and methylprednisolone pulse therapy. Rituximab was used as an add-on therapy in three patients. Five patients lost their graft within 2 years after kidney transplantation (rapid group). In contrast, three patients had much longer graft survival (nonrapid group). We compared the clinical characteristics of the rapid and nonrapid groups. Proteinuria tended to be lower in the nonrapid group at the third and subsequent months of therapy. The rapid group had persistent nephrotic syndrome. The rate of reduction in proteinuria was lower in the rapid group than in the nonrapid group. CONCLUSIONS: Our study suggests that persistent nephrotic syndrome and a low rate of reduction in proteinuria may predict rapid progression to graft failure in nonresponders.
Assuntos
Glomerulosclerose Segmentar e Focal , Sobrevivência de Enxerto , Transplante de Rim , Recidiva , Humanos , Glomerulosclerose Segmentar e Focal/terapia , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Criança , Adolescente , Pré-Escolar , Japão , Troca Plasmática , Resultado do Tratamento , Proteinúria/etiologia , Complicações Pós-Operatórias/etiologiaAssuntos
Taxa de Filtração Glomerular , Humanos , Adulto , Criança , Masculino , Feminino , Adolescente , Seguimentos , Adulto Jovem , Testes de Função Renal , Pré-Escolar , Prognóstico , Rim/fisiopatologia , Pessoa de Meia-Idade , LactenteRESUMO
Introduction: Since the implementation of the new selection criteria in 2018, kidney donations from pediatric patients have been prioritized for pediatric recipients and kidney donations from pediatric donors have increased in Japan. Herein, we present two cases of en bloc kidney transplantation. Case presentation: Case 1: A 19-year-old male patient who had been on hemodialysis for 5 years due to end-stage renal disease. After brain death, a graft from a 5-year-old boy was transplanted into the right iliac fossa. Case 2: A 19-year-old male patient, who had previously undergone a living kidney transplantation at the age of 3, received a secondary cadaveric kidney transplantation in the left iliac fossa. The graft was procured from a 17-month-old girl following cardiac death. Conclusion: This report will help surgeons perform en bloc kidney transplantation in the growing number of pediatric kidney donations, such as those in Japan.
RESUMO
Possible roles of anti-nephrin antibodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin antibodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cutoff 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin antibodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding.