Fedele Lasaponara

Lymphatic disorders after renal transplantation: new insights for an old complication

In renal transplanted patients, lymphoceles and lymphorrhea are well-known lymphatic complications. Surgical damage of the lymphatics of the graft during the procurement and of the lymphatic around the iliac vessels of the recipients has been associated with development of lymphatic complications. However, lymphatic complications may be related to medical factors such as diabetes, obesity, blood coagulation abnormalities, anticoagulation prophylaxis, high dose of diuretics, delay in graft function and immunosuppressive drugs. Consistently, immunosuppression regimens based on the use of mTOR inhibitors, especially in association with steroids and immediately after transplantation, has been associated with a high risk to develop lymphocele or lymphorrhea. In addition, several studies have demonstrated the association between rejection episodes and lymphatic complications. However, before the discovery of reliable markers of lymphatic vessels, the pathogenic mechanisms underlining the development of lymphatic complications during rejection and the influence of mTOR inhibitors remained not fully understood. The recent findings on the lymphatic systems of either native or transplanted kidneys together with the advances achieved on lymphangiogenesis shared some lights on the pathogenesis of lymphatic complications after renal transplantation. In this review, we describe the surgical and medical causes of lymphatic complications focusing on the rejection and immunosuppressive drugs as causes of lymphatic complications.

Phosphodiesterase Type 5 Inhibitor Treatment for Erectile Dysfunction in Patients with End-Stage Renal Disease Receiving Dialysis or After Renal Transplantation

INTRODUCTION The phosphodiesterase type 5 (PDE5) inhibitors are generally well tolerated and effective for treating erectile dysfunction (ED), including in patients with significant comorbidity. Because of this benign safety profile, investigators have used PDE5 inhibitors to treat patients with ED and severe renal disease or those who have received renal transplants. AIM To assess safety and efficacy of PDE5 inhibitors in patients receiving dialysis or renal transplants. MAIN OUTCOME MEASURES Erectile function as assessed by the International Index of Erectile Function (IIEF) and Global Assessment Questions; adverse events (AEs). METHODS We reviewed published studies of PDE5 inhibitors in patients receiving dialysis or renal transplants. RESULTS In double-blind, placebo-controlled studies in patients receiving dialysis or renal transplants, sildenafil significantly improved erectile function as assessed by the IIEF, and 75-85% of patients reported improved erectile function on Global Assessment Questions; efficacy was more variable in less well-controlled studies. In >260 patients undergoing dialysis who received sildenafil in clinical studies, there were only six reported discontinuations because of AEs (headache [N=3], headache and nausea [N=1], gastrointestinal [N=1], and symptomatic blood pressure decrease [N=1]). In approximately 400 patients with renal transplants who received sildenafil, only three patients discontinued because of AEs. Vardenafil improved IIEF scores of up to 82% of renal transplant recipients in randomized, controlled studies (N=59, total), with no reported discontinuations because of AEs. Limited data also suggest benefit with tadalafil. CONCLUSIONS ED is common in patients undergoing renal dialysis or postrenal transplant and substantially affects patient quality of life. Sildenafil and vardenafil appear to be efficacious and well tolerated in patients receiving renal dialysis or transplant.

Cystogenic potential of CD133+ progenitor cells of human polycystic kidneys†

In autosomal dominant polycystic kidney disease, cysts arise focally and disrupt normal renal tissue leading to renal failure. In the present study, we show that cyst‐lining cells express the stem cell marker CD133. CD133+ progenitor cells isolated from polycystic kidney, carrying mutations of PKD genes, showed a dedifferentiated phenotype similar to CD133+ progenitor cells from normal kidney. However, these cells were more proliferative and presented a defective epithelial differentiation phenotype with respect to normal renal CD133+ cells as they were not able to express all tubular epithelial cell markers when cultured in epithelial differentiation medium. Polycystic CD133+ cells, in contrast to normal renal CD133+ cells, formed cysts in vitro in a three‐dimensional culture system and in vivo when injected subcutaneously within Matrigel in SCID mice. Rapamycin treatment reduced in vitro proliferation of polycystic CD133+ cells and decreased cystogenesis both in vitro and in vivo. The in vitro epithelial differentiation was only partially improved by rapamycin. These results indicate that polycystic CD133+ cells retain a dedifferentiated phenotype and the ability to generate cysts. Copyright

Intraoperative superselective embolization of a biopsy-related arteriocalyceal fistula during a kidney transplantation.

A lthough macroscopic hematuria occurs in 3.4% to 10% of patients after renal transplant biopsies, major complications requiring invasive procedures are rare (1%). An arteriocalyceal fistula associated with severe gross hematuria has been reported in less than 0.1% of graft biopsies (1, 2). In such cases, an angiographic evaluation is indicated, and a superselective arterial embolization should be considered to save the kidney (3Y5). In the literature, some case reports describe the successful selective arterial embolization in arteriocalyceal fistulas caused by diagnostic biopsies performed for renal function impairment in transplanted kidneys (4, 6). To our knowledge, the case that we present is the first intraoperative treatment by superselective arterial embolization during a kidney transplantation of an arteriocalyceal fistula caused by a scoring biopsy on the graft performed at the moment of organ recovery.

Subcapsular Hematoma Causing Anuria After Renal Graft Trauma.

A 67-year-old man presented to the emergency department 22 hours after a trauma to his kidney graft. He was asymptomatic during the first 10 hours, then he became anuric. His serum creatinine level was 2.73 mg/dL (baseline, 0.7 mg/dL), and his hemoglobin concentration was 13.1 g/dL. Computer tomography showed a 4-cm subcapsular hematoma without active bleeding. He underwent urgent decompression of the hematoma, and we did not find any active bleeding or parenchymal laceration. Urinary output had already recovered by the end of surgery without early or late complications. In conclusion, subcapsular hematoma, complicating a traumatic event on a kidney graft, can lead to a progressive parenchymal compression resulting in anuria. So, although in the absence of anemia, such events require urgent surgical decompression. Symptoms cannot be immediate, so all the graft trauma should be investigated with early ultrasound. Little is known in the case of major renal trauma but mildly symptomatic. Probably surgical exploration is better than observation to prevent possible early and late complications such as organ rejection or a Page kidney.

[A 8-year-forgotten ureteral stent after kidney transplantation: treatment and long-term follow-up].

Introduction Forgotten indwelling ureteral stents can cause significant urological complications. Only few cases are reported after kindney transplantation. Materials and Methods We present a case of a 39-year-old woman, transplanted in 1993 and referred to our Transplant Center 8 years later, because of a serious urinary tract infection with renal function impairment. Abdominal CT scan showed pyelonephritis and hydronephrosis in the transplanted kidney and the presence of a calcific ureteral stent, which had been forgotten in situ for 8 years. The stent was removed, but it was impossibile to replace it with a new stent both retrogradely and anterogradely, because of a tight obstruction of the mid ureter. So a uretero-ureteral anastomosis with up urinary tract was performed. Results No intra- or post-operative complications occurred. At 9 years’ follow-up, the patient shows an optimal renal function, with no urinary tract infection. Discussion A forgotten ureteral stent in a trasplanted kidney can cause a lot of complications and can lead to graft loss. The prosthesis may cause an irreversibile ureteral damage, so, as in our experience, forgetting a ureteral stent can result in a complex surgery.