X-linked Alport syndrome in Hellenic families: phenotypic heterogeneity and mutations near interruptions of the collagen domain in COL4A5

The X-linked Alport syndrome (ATS) is caused by mutations in COL4A5 and exhibits a widely variable expression. Usually ATS is heralded with continuous microhematuria which rapidly progresses to proteinuria, hypertension and chronic or end-stage renal disease (ESRD) by adolescence, frequently accompanied by sensorineural deafness and ocular complications. Milder forms of ATS also exist. We studied 42 patients (19M, 23F) of nine Hellenic families suspected clinically of X-linked ATS who presented with marked phenotypic heterogeneity. We identified mutations in COL4A5 in six families. Two males with nonsense mutation E228X reached ESRD by ages 14 and 18. Frameshift mutation 2946delT followed the same course with early onset renal involvement and deafness. However, two males with the milder missense mutation G624D, reached ESRD after 39 years and one patient showed thin basement membrane nephropathy (TBMN). Another 5/8 affected males with missense mutation P628L also developed ESRD between 30 and 57 years, while three exhibit only mild chronic renal failure (CRF). The data support previous findings that certain mutations are associated with milder phenotypes and confirm that mutation G624D may be expressed as TBMN with familial hematuria. Similar conclusions apply for missense mutation P628L. Interestingly, mutations G624D and P628L are near the 12th natural interruption of COL4A5 triple helical domain, which may explain the milder phenotype.     

Focal segmental glomerulosclerosis and chronic kidney disease in pediatric patients

Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of acquired glomerular disease leading to end-stage kidney disease. Its incidence is rising around the world. There is no proven therapy for those patients who do not respond to corticosteroids and it can recur in 20% to 25% of patients who receive a kidney transplant. The disease can be primary, or it can be secondary to various conditions including vesicoureteral reflux, obesity, medications, and infections. Recent advances have demonstrated the important role of genetic mutations in podocyte proteins as a cause of FSGS. There is an urgent need for randomized clinical trials to develop safe and effective therapy for FSGS that occurs in the native or transplanted kidney.     

Lessons from studies on focal segmental glomerulosclerosis: an important role for parietal epithelial cells?

Glomerular diseases are caused by multiple mechanisms. Progressive glomerular injury is characterized by the development of segmental or global glomerulosclerosis independent of the nature of the underlying renal disease. Most studies on glomerular disease focus on the constituents of the filtration barrier (podocytes, glomerular basement membrane (GBM), endothelial cells) or the mesangial cells. Little attention is given to the epithelial cells lining Bowman's capsule, the so called parietal epithelial cells (PECs). This 'lack of attention' is partly explained by the presumed 'passive' function of PECs, which are large, flattened cells that cover Bowman's capsule in a single cell layer and form a barrier between the ultrafiltrate and the periglomerular interstitium, in normal glomerular physiology. A more important reason has been the lack of an established primary role for the parietal epithelium in glomerular diseases. However, in recent years, several studies have demonstrated that PECs are involved in extracapillary proliferation. In addition, PECs can become highly active, proliferating cells, expressing many growth factors, chemokines, cytokines, and their receptors. It was recently demonstrated that PECs also play a part in the development of focal segmental glomerulosclerosis (FSGS). This review summarises current knowledge of the PEC, with emphasis on the role of PECs in the development of FSGS.     

Recurrence of nephrotic syndrome/focal segmental glomerulosclerosis following renal transplantation in children

The incidence of recurrence of nephrotic syndrome/focal segmental glomerulosclerosis (NS/FSGS) is variable (~30%). The incidence of recurrence is less in African-Americans than in whites and Hispanics. Graft survival rates are decreased in recipients with FSGS, especially if remission of the NS is not achieved in those with recurrence. Although controversial, the use of living donor (LD) transplants are not contraindicated; however, obligatory heterozygote parental grafts with a podocin mutation should be used with caution. Optimal treatment to induce a remission post-transplant has not been delineated. Pre-transplant and/or prophylactic post-transplant pre-operative plasmapheresis (PP) for high-risk patients--especially those with recurrence in a previous graft--may be promising. An international multicenter controlled study is required to delineate the optimal approach to prevent and/or treat the recurrence of NS/FSGS.     

出生时五运六气与肾病综合征患儿病理类型的关系

目的 对比局灶节段性肾小球硬化(FSGS)和微小病变病理类型患儿出生日期的五运六气属性,探讨五运六气影响下的先天禀赋与病理类型的内在关联和差异,为临床判断预后及推测病理类型提供理论参考.方法 收集2005年1月1日至2019年12月31日广东省中医院儿科收治的住院病例中肾脏穿刺病理结果为FSGS和微小病变的患者54例,...