Jiyun Yang

Key molecular events in puromycin aminonucleoside nephrosis rats

Nephrin, podocin and α‐actinin are all involved in proteinuria, but it is unclear which molecular event plays a crucial role during the development of proteinuria. Immunofluorescence staining and real‐time quantitative polymerase chain reaction were used to study the glomerular expression of these molecules in puromycin aminonucleoside (PAN) nephrosis. Morphometric methods were applied to evaluate the podocyte foot process (FP) morphology. Two days after PAN injection, nephrin and podocin staining became discontinuous, podocin intensity decreased and FP swelled. Nephrin protein and mRNA decreased at day 5. Both podocin and nephrin intensity decreased dramatically when heavy proteinuria occurred, but nephrin mRNA was regained. When proteinuria disappeared, podocin recovered whereas nephrin did not (P = 0.02); α‐actinin intensity increased (P = 0.009) and the distribution changed. The podocyte FP volume density correlated negatively with nephrin (r = −0.78, P = 0.0001) and podocin immunofluorescence intensity (r = −0.76, P = 0.0001). We conclude that, before the onset of proteinuria, the first response was the nephrin and podocin distribution change, podocin protein decrease and swollen FP; the podocin quantitative change was earlier than nephrin. Podocin and nephrin distribution and the protein level was associated with proteinuria more closely than their mRNA level. The delayed α‐actinin induction might be a reparative response.

Expression of nephrin, podocin, α-actinin, and WT1 in children with nephrotic syndrome

Recently, nephrin, podocin, α-actinin, and WT1, which are located at the slit diaphragm and expressed by the podocyte, were found to be causative in congenital/familial nephrotic syndrome (NS), but their role in acquired NS remains unclear. We studied their expression in NS with the aim of disclosing their possible role in the development of proteinuria. Immunofluorescence, confocal microscopy, and image analysis were used to study the expression and the distribution in 19 children with primary NS, 9 with isolated hematuria, and 9 controls. All the children with NS presented with heavy proteinuria and foot process effacement was identified by electron microscopy. No proteinuria and foot process effacement was seen in the group with hematuria. A dramatic decrease of podocin expression was found in NS (86.66±22.74) compared with control groups (P=0.014). Furthermore, we also found the pattern of distribution of nephrin, podocin, and α-actinin changed in children with NS. In conclusion, a dramatic decrease of podocin expression and abnormal distribution of nephrin, podocin, and α-actinin were found in children with NS. No differences were found in children with isolated hematuria, suggesting involvement of these molecules in the development of proteinuria in primary NS.

Phenotypic and genotypic features of Alport syndrome in Chinese children

Abstract. Chinese Alport syndrome (AS) was analyzed in 44 unrelated patients who were screened for mutations in the COL4A5 gene by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis or PCR direct sequencing in 30 of the 44 patients. The clinical data showed that all patients had hematuria; 25 of 29 male patients (86%) and 9 of 15 female patients (60%) had proteinuria; 11 of 29 male patients (38%) and 1 of 15 female patients (7%) had nephrotic-level proteinuria; 10 of 21 male patients examined (48%) and 1 of 12 female patients examined (8%) had hearing abnormalities. Renal function remained normal despite hearing abnormalities, and ocular lesions occurred in 10%. Among 30 of 44 patients who had a family history of end-stage renal disease (ESRD), 80% (24/30) belonged to X-linked juvenile kindreds, and 20% (6/30) patients to adult kindreds. Of the 44 patients, 14 did not have a family history of ESRD, while 11 of 14 patients diagnosed with X-linked AS did. DNA analysis revealed four missense mutations, two silent mutations, one substitution, and one in-frame deletion. PCR along with Southern hybridization analysis revealed a large deletion of the paired COL4A5 and COL4A6 genes. Chinese AS patients were characterized clinically with hematuria, heavy proteinuria, and more juvenile forms. Mutations in these patients were usually small mutations, while a large deletion involving the 5′ part of both COL4A5 and COL4A6 genes was identified.

Non-ketotic hyperosmolar coma complicating steroid treatment in childhood nephrosis.

Two nephrotic children treated with prednisone developed steroid-induced diabetes and non-ketotic hyperosmolar coma (NKHC). Both patients presented with convulsions, coma and shock. The glucose concentration of the cerebrospinal fluid was 425 mg/dl and 622 mg/dl, respectively. Both patients had no diabetic family history, but had been treated with prednisone for 4 and 8 months, receiving total doses of 6.6 and 10.8 g, respectively. Despite conventional therapy, both patients deteriorated rapidly and died several hours later. Steroid-induced diabetes associated with NKHC is a rare but serious complication of steroid therapy.

The interaction of glomerular mesangial cells and epithelial cells

Abstract. The interaction of cells within the glomerulus plays an important role in the development and progression of glomerular disease. To investigate the interaction of glomerular mesangial cells (GMC) and epithelial cells (GEC), and mediator(s) of this interaction, we investigated the effect of Adriamycin (doxorubicin hydrochloride)-induced (ADR) rat GMC-conditioned medium (GMC-CM) on the incorporation of 35S, 3H-leucine, and 3H-thymidine in normal rat GEC, as well as 3H-thymidine uptake by normal rat GMC in response to ADR-rat GEC-CM. In addition, changes in the responsiveness to interleukin-6 (IL-6) and the products of IL-6 were assessed in ADR-rat GMC. The results showed that: (1) GMC-CM of ADR-rat with heavy proteinuria stimulated GEC proliferation and the synthesis of sulfated compounds and protein, while the GEC-CM of ADR-rat from the same nephrotic period increased GMC proliferation; (2) the ADR-rat GMC had altered responsiveness to IL-6 and its products. The stimulation index results demonstrated the interaction of GMC and GEC in the ADR-induced rat model, and that this interaction related closely to the degree of proteinuria and was mediated by soluble products of the damaged glomerular cell.

Alport syndrome with neurofibromatosis type-I: a case report.

Abstract. We report a 9-year-old boy with repeated fractures of the tibia from age 6 months and microscopic hematuria from age 2 years. His maternal family has a history of nephritis and his paternal family has neurofibromatosis type-I (NF-I). The boy’s renal biopsy revealed an irregular attenuation and splitting of the glomerular basement membrane. The skin biopsy was stained with monoclonal antibody against the α5 chain of type IV collagen; the epidermal basement membrane was negative in the boy and segmentally positive in the boy’s mother. We conclude that the patient inherited Alport syndrome from his mother and NF-I from his father. We postulate this was a chance association and that this case does not suggest any relationship between the two diseases.

Effects of Losartan on Fibrinolytic Parameters and von Willebrand Factor in Chinese Subjects with Hypertension: A Comparative Study versus Atenolol

To compare the effects of losartan and atenolol on plasma fibrinolytic parameters and von Willebrand factor (vWF), Chinese subjects with mild-to-moderate hypertension were randomized to receive losartan (50 mg/day; n = 30) or atenolol (50 mg/day; n = 30) for 8 weeks. If target blood pressure (< 140/90 mmHg) was not achieved at week 4, hydrochlorothiazide (12.5 mg/day) was also administered. Plasma levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and vWF were determined at baseline and after treatment. Between-group baseline characteristics and blood pressure decrease were comparable. Losartan significantly reduced plasma PAI-1 and vWF and PAI-1/tPA ratio. Atenolol significantly increased plasma tPA, but PAI-1, vWF and PAI-1/tPA ratio were unchanged. In conclusion, losartan, but not atenolol improved the fibrinolytic system and reduced plasma vWF levels in Chinese hypertensives.