No abstract

Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to renal failure. Mutations in polycystin-1 (PC1) underlie most cases of ADPKD, but the function of PC1 has remained poorly understood. No preventive treatment for this disease is available. Here, we show that the cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is inappropriately activated in cyst-lining epithelial cells in human ADPKD patients and mouse models. Rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in two independent mouse models of PKD. Treatment of human ADPKD transplant-recipient patients with rapamycin results in a significant reduction in native polycystic kidney size. These results indicate that PC1 has an important function in the regulation of the mTOR pathway and that this pathway provides a target for medical therapy of ADPKD.rapamycin ͉ renal epithelial cells ͉ tuberin A utosomal-dominant polycystic kidney disease (ADPKD) is one of the most common human monogenic diseases and affects 12 million people worldwide (for recent reviews, see refs.

Early experience with laparoscopic partial nephrectomy is promising. Laparoscopic partial nephrectomy offered the advantages of less operative time, decreased operative blood loss and a shorter hospital stay. When applied to patients with a single renal tumor 7 cm or less, laparoscopic partial nephrectomy was associated with additional postoperative morbidity compared to open partial nephrectomy. However, equivalent functional and early oncological outcomes were achieved.

Partial nephrectomy is effective for localized renal cell carcinoma, providing long-term tumor control with preservation of renal function.

Nephron sparing surgery provides effective therapy for patients in whom preservation of renal function is a relevant clinical consideration. The importance of meticulous operative technique for achieving acceptable oncological and functional outcomes is emphasized. Accumulating data in appropriately select patients suggest a long-term functional advantage gained by the maximal preservation of unaffected renal parenchyma without sacrificing cancer control.

Lower preoperative glomerular filtration rate, solitary kidney, older age, gender, tumor size and longer ischemic interval all predicted lower glomerular filtration rate after partial nephrectomy. Therefore, duration of renal ischemia is the strongest modifiable surgical risk factor for decreased renal function after partial nephrectomy, and efforts to limit ischemic time and injury should be pursued in open and laparoscopic partial nephrectomy.

Calcineurin inhibitor drug avoidance with basiliximab induction and sirolimus provides comparable 1-year transplant outcomes, with significantly better renal function in primary renal allograft recipients.

Following nephron sparing surgery for localized sporadic renal cell carcinoma cancer-free survival is significantly better in patients with tumors 4 cm. or less compared to those with larger tumors. The usefulness of the current TNM staging system can be improved by subdividing T1 tumors into T1a (4 cm. or less) and T1b (4 to 7 cm.).