Vascular endothelial growth factor (VEGF) is a potent promoter of endothelial mitogenesis and of endothelial permeability. Within the kidney it is synthesized primarily in the visceral glomerular epithelial cells (vGECs); however, the role of VEGF in the glomerulus remains unknown, as does the target cell upon which it acts. Although the target cells may be those of the glomerular endothelium, there are micro-anatomical reasons why this might not be the case. This, therefore, led us to consider the possibility that glomerular VEGF may bind to the vGECs themselves. Since it has been shown that vGECs do not express the main tyrosine kinase VEGF receptors, we chose to study vGEC expression of the more recently described VEGF isoform-specific receptors, the neuropilins. The expression of mRNAs for neuropilin-1, neuropilin-2 and soluble neuropilin was studied in whole kidney, sieved glomeruli and cultured podocytes by reverse transcription-PCR, and neuropilin-1 mRNA expression in isolated single glomeruli was analysed by nested reverse transcription-PCR. The expression of neuropilin-1 protein was investigated in cultured vGECs by Western blotting and immunocytochemistry, and in normal kidney sections by immunohistochemistry. Neuropilin-1 mRNA was detected in whole kidney, single and sieved glomeruli and cultured vGECs. Neuropilin-1 protein was detected in cultured vGECs and in vGECs in normal kidney sections by immunohistochemistry. Thus the present study suggests that vGECs may have the potential to bind the VEGF that they secrete. Functional studies will be required to address the potential significance of this finding in terms of an autocrine loop or VEGF sequestration.

Visceral glomerular epithelial cells (GECs) are involved in the maintenance of the filtration barrier and may play a role in immune responses. Cytokines may act on GECs and we wished to test this in vitro. Vascular endothelial growth factor (VEGF) is a specific product of the GEC that may play a role in glomerular permeability. We have investigated whether GECs in culture express receptors for interleukin (IL)-4, 10 and 13 (often grouped together as type 2 cytokines) and whether these cytokines alter GEC VEGF production. Type 2 cytokines were compared to transforming growth factor-β (TGF-β) and IL-1β which are known to upregulate VEGF production. GECs were grown from human nephrectomy specimens and cultured with and without the addition of exogenous cytokines. Messenger RNA data demonstrated the presence of IL-4 receptor α, IL-10 receptor 1 and 2, and IL-13 receptors α₁ and α₂. However, at the protein level by flow cytometry, only IL-13 α₂ could be consistently demonstrated. IL-4, IL-10 and IL-13 inhibited production of VEGF but did not affect the pattern of isoform expression. In contrast, TBF-β and IL-1β caused an increase in VEGF production. These effects were not explained by effects on proliferation. Our data provide evidence that GECs express receptors for type 2 cytokines and that these cytokines can act directly on GECs, to decrease VEGF production.

No abstract

Minimal change nephropathy (MCN) is an important cause of nephrotic syndrome, especially in children, that is strongly associated with atopy and IgE production. The immunogenetics of MCN are poorly understood. Interleukin-4 (IL-4) is the critical cytokine involved in the development of atopy. Polymorphic regions in the genes encoding IL-4 itself and the IL-4 receptor have been demonstrated that may predispose to increased activity. We have analysed these polymorphisms in 149 patients with MCN and 73 controls to test the hypothesis that these loci are involved in genetic predisposition to MCN. In our populations there were no polymorphisms in the IL-4 promoter. We did confirm allelic variation in a dinucleotide repeat in the second intron of the IL-4 gene, but there was no significant difference between allele distributions in MCN and controls. Similarly, allele frequencies for the IL-4 receptor alpha chain polymorphism were similar in patients and controls. Genetic loci which are believed to influence IL-4 responsiveness and to predispose to atopy do not appear to be associated with susceptibility to MCN.

In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.

No abstract

Minimal change nephropathy (MCN) is an important cause of nephrotic syndrome, especially in children, that is strongly associated with atopy and IgE production. The immunogenetics of MCN are poorly understood. Interleukin-4 (IL-4) is the critical cytokine involved in the development of atopy. Polymorphic regions in the genes encoding IL-4 itself and the IL-4 receptor have been demonstrated that may predispose to increased activity. We have analysed these polymorphisms in 149 patients with MCN and 73 controls to test the hypothesis that these loci are involved in genetic predisposition to MCN. In our populations there were no polymorphisms in the IL-4 promoter. We did confirm allelic variation in a dinucleotide repeat in the second intron of the IL-4 gene, but there was no significant difference between allele distributions in MCN and controls. Similarly, allele frequencies for the IL-4 receptor alpha chain polymorphism were similar in patients and controls. Genetic loci which are believed to influence IL-4 responsiveness and to predispose to atopy do not appear to be associated with susceptibility to MCN.

Study design: A Case Report of renal milk of calcium in a tetraplegic subject. Objectives: To increase the awareness of renal milk of calcium in spinal cord injury (SCI) physicians. Renal milk of calcium contains a colloidal suspension of calcium crystals. Since upright views of the kidneys are not performed in tetraplegic subjects, the renal milk of calcium may be misinterpreted as renal lithiasis by routine radiography taken in supine position. Setting: Regional Spinal Injuries Centre, Southport, England. Method: In a 41-year-old male with traumatic tetraplegia, X-ray of abdomen in supine position showed multiple opacities in the region of the left kidney. These radio opaque shadows were interpreted as renal calculi. Subsequently, computed tomography (CT) of the kidneys was performed. Results: CT con®rmed the presence of calculi in the mid-polar calyx. However, the density situated in the inferior calyx of the hydronephrotic left kidney exhibited a horizontal upper edge. This speci®c radiological ®nding as observed in the CT of kidneys, provided the clue to the presence of milk of calcium in the inferior calyx of the hydronephrotic left kidney. Conclusion: As plain ®lm of the abdomen in standing position is not performed in SCI patients, physicians caring for SCI patients should have a high index of suspicion for renal milk of calcium. Prompt diagnosis of renal milk of calcium will help to avoid unnecessary surgery, or extracorporeal shock wave lithotripsy. Spinal Cord (2000) 38, 325 ± 326