van Willem Son

Nephrectomy Elicits Impact of Age and BMI on Renal Hemodynamics: Lower Postdonation Reserve Capacity in Older or Overweight Kidney Donors

Renal functional reserve could be relevant for the maintenance of renal function after kidney donation. Low‐dose dopamine induces renal vasodilation with a rise in glomerular filtration rate (GFR) in healthy subjects and is thought to be a reflection of reserve capacity (RC). Older age and higher body mass index (BMI) may be associated with reduced RC. We therefore investigated RC in 178 consecutive living kidney donors (39% males, age 48 ± 11 years, BMI 25.5 ± 4.1). RC was determined as the rise in GFR (125I‐iothalamate), 4 months before and 2 months after donor nephrectomy. Before donor nephrectomy, GFR was 114 ± 20 mL/min, with a reduction to 72 ± 12 mL/min after donor nephrectomy. The dopamine‐induced rise in GFR of 11 ± 10% was reduced to 5 ± 7% after donor nephrectomy (p < 0.001). Before donor nephrectomy, older age and higher BMI did not affect reserve capacity. After donor nephrectomy, the response of GFR to dopamine independently and negatively correlated with older age and higher BMI. Moreover, postdonation reserve capacity was absent in obese donors. The presence of overweight had more impact on loss of RC in younger donors. In conclusion, donor nephrectomy unmasked an age‐ and overweight‐induced loss of reserve capacity. Younger donors with obesity should be carefully monitored.

PTLD visualization by FDG-PET : Improved detection of extranodal localizations

Post-transplant lymphoproliferative disease (PTLD) is a rare, but serious and potentially lethal complication of solid organ transplantation. It encompasses a heterogeneous group of diseases, ranging from Epstein–Barr virus driven polyclonal proliferations resembling infectious mononucleosis, to highly aggressive monomorphic proliferations indistinguishable from aggressive types of lymphoma (1). At diagnosis, patients are usually staged according to conventional diagnostic methods routinely applied for malignant lymphoma, including whole body computer tomography (CT) scanning and bone marrow biopsy (2). Although PTLD characteristically involves extranodal sites, these localizations may not always be visualized by CT scanning (3). Fluorodeoxyglucose (FDG)-positron emission tomography (PET) is a whole body imaging technique allowing functional characterization of hypermetabolic tissues by showing increased uptake of FDG at these sites. It has already been shown that FDG-PET provides significant additional information for the detection and staging of malignant lymphoma (4). We wondered whether FDG-PET would be as useful in PTLD as it is in aggressive lymphoma, and evaluated its value in the staging and treatment evaluation of histologically confirmed PTLD in 12 kidney transplant recipients observed between January 2000 and June 2004.

Uptake of pp65 in in vitro generated pp65-positive polymorphonuclear cells mediated by phagocytosis and cell fusion?

Objective: The cytomegalovirus (CMV) antigenemia consists of the detection of CMV pp65 in the nucleus of polymorphonuclear granulocytes (PMN), but it is unclear where and how PMN pick up virus particles or proteins. In an in vitro model for CMV antigenemia we investigated the mechanism of pp65 uptake by PMN that results in its expression in the nucleus. Methods: A series of inhibitors of different mechanisms was used to study the uptake of pp65 by PMN during coculture with CMV-infected endothelial cells and we performed a morphological analysis by light and transmission electron microscopy. Results: Nocodazole and cytochalasin B inhibited uptake of pp65 by PMN with 59.4 ± 14.1 and 73.3 ± 12.7%, respectively. The presence of anti-CMV hyperimmune globulin or lactoferrin during coculture reduced the number of pp65-positive PMN with 45.8 ± 7.0 or 40.6 ± 3.2%. Furthermore, a small number of the pp65-positive PMN obtained after coculture had fused to large cells with multilobed nuclei. PMN were observed that enclosed viral particles as well as free viral particles containing PMN in the cytoplasm. Conclusion: Fusion of viral particles with PMN and phagocytosis are both involved in the uptake of pp65.

Overcoming the problem of cytomegalovirus infection after organ transplantation: Calling for Heracles?

Although diagnosis of CMV infections and treatment of CMV disease with effetive antiviral drugs have become much easier, the persistent problem of CMV infection after solid-organ transplantation still requires solid knowledge of the pathophysiology of its clinical manifestations in order to minimize the impact of CMV infections in the future. The complex symptomatology of CMV infection after solid-organ transplantation is reviewed as well as some of the new theories attempting to explain the myriad of symptoms seen after transplantation.

Subclinical pneumonitis during cytomegalovirus infection after kidney transplantation

ABSTRACT In addition to life-threatening pneumonia, cytomegalovirus (CMV) may also causesubclinical pulmonary dysfunction after kidney transplantation. To investigate therole of plugging of cytomegalic endothelial cells (CEC) in the pulmonary capillarybed we prospectively determined specific carbon monoxide diffusion capacity(KCOc), and its components: the pulmonary diffusing membrane factor (Dm) andpulmonary capillary blood volume (Vcap) before and during CMV infection in 13kidney transplant recipients and 13 controls.During CMV infection median KCOc decreased significantly due to a decrease inboth Vcap and Dm. We illustrate the course of pulmonary diffusion in a male kidneytransplant recipient with CMV infection.We conclude that kidney transplant recipients with CMV infection have signi-ficant pulmonary diffusion disturbances due to a combination of lower Vcap andlower Dm. The most likely explanation for this phenomenon is a local inflammatoryprocess due to CMV and not plugging of cytomegalic endothelial cells.

Complement mediated renal inflammation induced by donor brain death

Kidneys retrieved from brain‐dead donors have impaired allograft function after transplantation compared to kidneys from living donors. Donor brain death (BD) triggers inflammatory responses, including both systemic and local complement activation. The mechanism by which systemic activated complement contributes to allograft injury remains to be elucidated. The aim of this study was to investigate systemic C5a release after BD in human donors and direct effects of C5a on human renal tissue. C5a levels were measured in plasma from living and brain‐dead donors. Renal C5aR gene and protein expression in living and brain‐dead donors was investigated in renal pretransplantation biopsies. The direct effect of C5a on human renal tissue was investigated by stimulating human kidney slices with C5a using a newly developed precision‐cut method. Elevated C5a levels were found in plasma from brain‐dead donors in concert with induced C5aR expression in donor kidney biopsies. Exposure of precision‐cut human kidney slices to C5a induced gene expression of pro‐inflammatory cytokines IL‐1 beta, IL‐6 and IL‐8. In conclusion, these findings suggest that systemic generation of C5a mediates renal inflammation in brain‐dead donor grafts via tubular C5a‐C5aR interaction. This study also introduces a novel in vitro technique to analyze renal cells in their biological environment.

A randomized clinical trial of living donor nephrectomy

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini‐open muscle splitting incision (MSI) technique and the transperitoneal hand‐assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0–44) vs. 15 (0–70), P = 0.043] and day 3 [7 (0–28) vs. 10 (0–91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0–73) vs. 42 (6–86), P = 0.001], day 7 [8 (0–66) vs. 33 (3–76), P < 0.001] and day 14 [2 (0–17) vs. 12 (0–51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND‐36, reduced costs and reduced CRP and IL‐6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy.