To investigate whether age at onset of steroid-sensitive nephrotic syndrome (SSNS) is predictive of subsequent relapses, or influences outcome, we retrospectively studied 60 patients who were under 10 years of age at onset and were followed for over 10 years. They were divided into three groups according to age at diagnosis: group 1-3 (1.0-3.9 years at onset, n=24), group 4-6 (4.0-6.9 years at onset, n=22), and group 7-9 (7.0-9.9 years at onset, n=14). In the 51 patients with long-term remission, defined as remaining relapse-free over 3 years, the total number of relapses was significantly more in group 1-3 (n=18) than in group 4-6 (n=19), and the interval between onset and long-term remission was significantly longer. Group 4-6 and group 7-9 had fewer patients with active disease at 10 years, follow-up than group 1-3, as assessed by the Kaplan-Meier method. These data suggest that the age at onset of SSNS influences the clinical course (i.e., frequency of relapses) and the time to reach long-term remission. An age of less than 4 years at onset of SSNS is associated with greater likelihood for frequent relapses and a greater time interval to attain long-term remission.

Partial trisomy distal 4q (denoted 4q+) is a human chromosomal disorder caused by duplication of the distal end of the long arm of chromosome 4 (Chr4). This disorder manifests typical phenotypes, including craniofacial, renal, heart and thumb developmental defects. Although these clinical features are likely caused by a dosage imbalance in the gene network involving the trisomic region, the causative gene or genes and the molecular bases are largely unknown. Here, we report mouse Recombination-induced mutation 4 (Rim4) as a model animal of 4q+. The Rim4 genome contains an insertion of a 6.5 Mb fragment from mouse chromosome 8 into chromosome 6. This insertion fragment contains 17 genes, including Hand2, that encode the basic helix-loop-helix transcription factor and is syntenic to the distal end of human Chr4, 4q32.3 to 4q34.1, which is responsible for 4q+. A comparison of phenotypes between patients with Rim4 and 4q+ revealed that Rim4 shows direct parallels with many phenotypes of 4q+ such as craniofacial, heart, cervical vertebra and limb deformities. Rebalancing the gene dosage by a genetic cross with Hand2 knockout mice ameliorated symptoms of the heart and limb deformities of Rim4. Conversely, an increase in copy number of Hand2 in wild-type mice recaptures the heart and limb deformities of Rim4. Our results collectively demonstrate that overdosage of Hand2 is a major cause for at least the limb and heart phenotypes of 4q+ and that mouse Rim4 provides a unique animal model for understanding the molecular bases underlying the complex phenotypes of 4q+.

The effect on the kidney capillaries of T lymphocyte culture supernatants from patients with minimal change nephrotic syndrome was studied by infusion into the left renal artery of rats. The supernatants of T lymphocyte cultures from nephrotic patients induced significant proteinuria and a reduction of anionic sites in the glomerular basement membrane of the kidneys in the rats. These changes were not produced in rats receiving equivalent supernatants from healthy controls.

We report on two sibs with partial 4q trisomy: dup (4)(q35.2-q31.22) and their renal biopsy findings. Both of them show renal hypoplasia, although their chromosomal aberration lacks the minimal duplicated region 4q22-q23 and/or 4q25-q31.3, which had been shown to be associated with urogenital abnormalities and thumb malformations in previous reports. From the renal biopsy findings, the two sibs were diagnosed as oligonephronia. We summarize the 13 having published cases of duplication of chromosome 4q, and examine which segments have a close relationship to renal hypoplasia. We suggest that renal hypoplasia may be female-prone, and may have a close relationship with duplication of 4q33-q34.

These data indicate that the prognosis of APSGN during childhood is excellent, when adequately diagnosed and treated.

IGFBP-2, -7, -8 and -10 are produced by normal and injured glomerular podocytes and may regulate local IGF-I actions in podocytes and/or cortical tubular cells in the kidney.

Peripheral T lymphocytes from patients with minimal change nephrotic syndrome (MCNS) and controls were treated for their ability to produce vascular permeability factors (VPF) without concanavalin A stimulation. In vitro cultures of T lymphocytes from active MCNS produced VPF in the supernatant, whereas T lymphocytes from inactive MCNS or normal subjects did not. Furthermore, the plasma from patients with active MCNS markedly inhibited VPF production when compared with plasma taken from inactive MCNS or fetal calf serum alone. However, the plasma from MCNS in neither the active nor the inactive stage had any direct blocking effect on VPF activity. These results seem to suggest that the plasma from patients with MCNS in the active stage inhibits VPF production, but does not neutralize T lymphocytes derived VPF activity.

Since it has been demonstrated that decreased urinary calbindin 1 levels are indicative of decreased calbindin 1 kidney expression due to distal nephron segment injuries, calbindin 1 might be a useful urinary biomarker for identifying distal nephron segment injuries.