W J. van Son

Predictive capacity of pre-donation GFR and renal reserve capacity for donor renal function after living kidney donation

Kidney transplantation from living donors is important to reduce organ shortage. Reliable pre‐operative estimation of post‐donation renal function is essential. We evaluated the predictive potential of pre‐donation glomerular filtration rate (GFR) (iothalamate) and renal reserve capacity for post‐donation GFR in kidney donors.

Complement mediated renal inflammation induced by donor brain death : role of renal C5a-C5aR interaction

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.

Uninfected and cytomegalic endothelial cells in blood during cytomegalovirus infection: effect of acute rejection.

After transplantation, human cytomegalovirus (HCMV) infections can cause vascular damage to both the graft and the host. To study a possible relationship between the degree of vascular injury, clinical symptoms of HCMV infection, and transplant rejection, the appearance and numbers of endothelial cells (ECs) in blood of 54 kidney transplant recipients were investigated in a prospective clinical study. Two types of endothelial cells were identified: cytomegalic ECs (CECs) were detected in patients with moderate or high HCMV antigenemia, and uninfected ECs were observed in patients with and without HCMV infection. The incidence of either CECs, ECs, or the combination of both was associated with HCMV-related clinical symptoms (P<.01). Remarkably, the occurrence of rejection episodes before HCMV infection was an important risk factor for the occurrence of ECs in blood (ECs, CECs, or both) during HCMV infection (P<.001).

Pulmonary involvement during cytomegalovirus infection in immunosuppressed patients

Abstract: Although cytomegalovirus (CMV) pulmonary involvement after solid organ transplantation is infrequently seen nowadays, CMV pneumonitis is still a potential lethal complication. Introduction of the pp65 antigenemia assay enabled early and rapid diagnosis of CMV viremia in transplant patients prior to symptoms. Also, in asymptomatic patients with CMV viremia, a decreased pulmonary diffusion capacity could be demonstrated. In this review, we discuss clinical and subclinical pulmonary involvement of CMV infection in the immunocompromised host with an emphasis on transplant recipients. The clinical course, diagnosis, therapy, prophylaxis, and pathophysiology of CMV pneumonitis are discussed.

Impact of Depression on Long-Term Outcome After Renal Transplantation: A Prospective Cohort Study

Background Renal transplantation is the treatment of choice for end stage renal disease. Although there is more depression in wait-listed versus transplant patients, depression persists after transplantation. We investigated the determinants of depression in renal transplantation recipients (RTRs) and the association with cardiovascular (CV) and all-cause-mortality and graft failure. Methods RTR were investigated between 2001 and 2003. Depression was assessed using the Depression Subscale of the Symptom Checklist (SCL-90). Mortality and graft failure were recorded until May 2009. Results A total of 527 RTR (age, 51±12 years; 55% men) were studied; 31% of the RTR were indicated with depression. Independent variables associated with depression were medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration. During follow-up for 7.0 (6.2–7.5) years, 114 RTR (59 CV) died. In Cox regression analyses, depression was strongly associated with increased risk for CV (HR=2.12 [1.27–3.53], P=0.004) and all-cause mortality (HR=1.96 [1.36–2.84], P<0.001). Adjustments for confounders did not materially change these associations. The association with graft failure (HR=1.77 [1.01–3.10]. P=0.047) disappeared after adjustment for kidney function (P=0.6). Conclusions Although our study has several limitations, including the lack of pretransplant depression status, we identified medically unfit for work, proteinuria, lower physical activity level, and longer dialysis duration as independent variables associated with depression. We furthermore found that depression is associated with CV and all-cause mortality in RTR.

Effects of changing immunosuppressive regimen on the incidence, duration, and viral load of cytomegalovirus infection in renal transplantation : a single center report

Abstract: Background. In this retrospective single center study we have evaluated the relation between the immunosuppressive regimen and the incidence and characteristics of cytomegalovirus (CMV) infection in the setting without CMV prophylaxis from 1989 through 1998. Methods. All (470) first cadaveric renal transplantations in nonsensitized (PRAu2003<u200360%) patients were analyzed. Immunosuppression consisted of cyclosporine A (Sandimmune) and prednisolone from 1989 through 2‐1993 (S; 189 patients), of cyclosporine microemulsion (Neoral) and prednisolone from 3‐1993 through 5‐1997 (N; 200 patients) and of mycophenolate mofetil, Neoral and prednisolone from 5‐1997 until 1998 (M; 81 patients). The CMV pp65‐antigenemia was measured routinely at least once weekly from day 10 till 12u2003weeks after transplantation or until pp65‐antigenemia became negative. No CMV‐prophylaxis was given. Results. By changing from Sandimmune to Neoral and by adding mycophenolate mofetil, respectively, we observed a higher frequency of especially secondary CMV infections (S vs. N vs. M, respectively, 28 vs. 50 vs. 63%, Pu2003=u20030.026; S vs. N, Pu2003=u20030.027; S vs. M, Pu2003=u20030.015; and N vs. M, n.s). The CMV infections lasted longer (median duration antigenemia S vs. N vs. M, respectively, 3 vs. 5 vs. 7u2003weeks, Pu2003=u20030.0003; S vs. N, Pu2003<u20030.002; S vs. M, Pu2003<u20030.001; and N vs. M, Pu2003<u20030.05). Viral load was higher in M (median maximal pp65‐antigenemia S vs. N vs. M, respectively, 19 vs. 14.5 vs. 73, Pu2003<u20030.01; S vs. N, n.s.; S vs. M, Pu2003<u20030.001 and N vs. M, Pu2003<u20030.01). Conclusions. The use of Neoral and the addition of mycophenolate mofetil caused significant changes in the incidence, duration and viral load of CMV infections.

The predictive value of renal vascular resistance for late renal allograft loss.

The renal artery resistance index (RI), assessed by Doppler ultrasonography, was recently identified as a new risk marker for late renal allograft loss. This finding requires confirmation since RI in that study was not measured at predetermined time points and ultrasonography is operator‐dependent. We investigated the predictive value of renal vascular resistance (RVR), a less operator‐dependent method as assessed by mean arterial pressure divided by renal blood flow, for the prediction of recipient mortality and death‐censored graft loss. RVR was compared to commonly used risk markers such as creatinine clearance (CrCl), serum creatinine (SCreat) and proteinuria (UProt) in 793 first‐time cadaveric renal transplant recipients at predetermined time points after transplantation using receiver operating characteristics (ROC) and Cox survival analyses. The present study showed that RVR is a prominent risk marker for recipient mortality and death‐censored graft loss. However, the predictive value of RVR for recipient mortality owed mainly to the impact of mean arterial blood pressure. In contrast, RVR constituted more than the sum of its components for death‐censored graft loss, but showed less predictive value than SCreat in univariate analysis. As the assessment of RVR is expensive and time‐consuming, we believe that RVR holds no clinical merit for the follow‐up of renal transplant recipients.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic 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), Pu2003=u20030.043] and day 3 [7 (0–28) vs. 10 (0–91), Pu2003=u20030.023] and lower VAS scores while coughing on postoperative day 3 [20 (0–73) vs. 42 (6–86), Pu2003=u20030.001], day 7 [8 (0–66) vs. 33 (3–76), Pu2003<u20030.001] and day 14 [2 (0–17) vs. 12 (0–51), Pu2003=u20030.009]. 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.

An intrarenal abscess as presenting symptom of an infection with Nocardia farcinica in a patient after renal transplantation

Abstract: A 52‐year‐old man presented 8 months after transplantation with an intrarenal mass, which proved to be caused by an infection with Nocardia farcinica. Because of the potential fatal course of nocardiosis, transplantectomy was performed and long‐term antibiotic treatment was instituted. Three‐and‐a‐half years later, this patient underwent successful re‐transplantation under co‐trimoxazole prophylaxis. At present, more than 1 year after his second transplant has been performed, there are no signs of recurrence of Nocardia infection. To our knowledge, this is the first report of a patient with nocardiosis with an intrarenal abscess as presenting symptom.

Complement Mediated Renal Inflammation Induced by Donor Brain Death: Role of Renal C5a-C5aR Interaction: Renal C5a-C5aR Interaction in 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.