Rapid Dynamics of Polyomavirus Type BK in Renal Transplant Recipients

BackgroundPolyomavirus type BK-associated nephropathy (PVAN) is an emerging cause of early renal transplant failure. No specific antiviral treatment has been established. Current interventions rely on improving immune functions by reducing immunosuppression. In patients with PVAN, a high BK virus (BKV) load is detectable in plasma. However, the relationship between BKV replication and disease is not well understood MethodsIn a retrospective analysis of BKV plasma load in renal transplant recipients undergoing allograft nephrectomy (n=3) or changes in immunosuppressive regimen (n=12), we calculated viral clearance rates and generation times and estimated the loss of BKV-infected renal cells ResultsAfter nephrectomy, BKV clearance was fast (viral half-life [t 1/2], 1-2 h) or moderately fast (t 1/2, 20-38 h), depending on the sampling density, but it was independent of continued immunosuppressive regimens. After changing immunosuppressive regimens, BKV was cleared with a t 1/2 of 6 h-17 days. Using the basic reproductive ratio, the efficacies of intervention ranged from 7% to 83% (mean, 28%; median, 22%) ConclusionThe results emphasize that high-level BKV replication is a major pathogenetic factor that may have implications for genome rearrangements, immune evasion, and antiviral resistanc

Effect of l-carnitine on the kinetics of carnitine, acylcarnitines and butyrobetaine in long-term haemodialysis

Background. The current study was performed to investigate the kinetics of carnitine, individual acylcarnitines and butyrobetaine in patients on haemodialysis. Methods. Eight stable long-term haemodialysis patients were studied under basal conditions (no carnitine supplementation) and 3 weeks after intravenous supplementation with l-carnitine (10 or 20 mg/kg body weight) after each haemodialysis session. The kinetic studies included serial determinations of carnitine and metabolites just before, during or between haemodialysis sessions. Analysis was performed by liquid chromatography-tandem mass spectrometry. Results. Before haemodialysis, the plasma concentrations were (µmol/l) 15.1±0.6 (mean±SEM) for carnitine, 5.9±0.7 for acetylcarnitine, 0.66±0.04 for propionylcarnitine and 0.98±0.08 for butyrobetaine (basal conditions) or 142±23 for carnitine, 69±12 for acetylcarnitine, 6.0±1.1 for propionylcarnitine and 2.6±0.3 for butyrobetaine (carnitine 20 mg/kg). During haemodialysis, the plasma concentrations dropped by ∼80% for all compounds determined, with extraction coefficients ranging from 0.65 to 0.86. In patients supplemented with 20 mg/kg carnitine, the amount of carnitine removed by haemodialysis equalled 42% of the dose administered, consisting of 2.08 mmol carnitine, 1.03 mmol acetylcarnitine and 0.051 mmol propionylcarnitine. Between the haemodialysis sessions, carnitine, acylcarnitines and butyrobetaine reached apparent steady-state concentrations within 1 day both under basal conditions and after supplementation. Conclusions. Patients on haemodialysis have reduced carnitine, acylcarnitine and butyrobetaine plasma levels, which can be increased by supplementing carnitine. Propionylcarnitine, an important constituent of the acylcarnitine pool, can be removed by haemodialysis. Removal of potentially toxic acyl-groups may represent a mechanism for a beneficial effect of carnitine in these patient

Haemolytic uraemic syndrome caused by factor H mutation: is single kidney transplantation under intensive plasmatherapy an option?

Complement factor H (CFH) mutation is one of the causes of atypical haemolytic uraemic syndrome (aHUS). Patients with CFH mutation-associated aHUS progress often to end-stage renal disease despite plasma exchange therapy. When such patients are transplanted, aHUS recurs almost invariably and causes graft failure making the rationale of single kidney allograft transplantation questionable. Since CFH is synthesized mostly by the liver, combined liver-kidney transplantation has been recommended. However, fatal outcomes have been reported using this strategy. We report a case of successful single kidney allograft transplantation in a patient with a CFH gene mutation (R1210C), who had end-stage renal failure after three flares of aHUS treated with plasma exchange. He received peri- and postoperative infusions of fresh frozen plasma, which to date has prevented recurrence of the disease. He has preserved renal function 1-year post-transplan

Rapid adaptation of the intrarenal resistance index after living donor kidney transplantation

Background. Limited data exist concerning changes of renal perfusion directly after kidney transplantation. Colour-coded duplex sonography is the accepted method to assess kidney perfusion after transplantation. A widely used, although unspecific, Doppler parameter is the intrarenal resistance index (RI). The aim of this study was to clarify the influence of different patient- and procedure-related factors on RI before and immediately after living kidney transplantation. Methods. In a prospective study, 80 living kidney transplantation donor-recipient pairs were included. RI was measured in the donor 1 to 3 days before nephrectomy and in the recipient during the first hour after transplantation to examine the influence of age, heart rate, duration of cold and warm ischaemia time and immunosuppressive medications. Results. Mean RI did not differ between donors and recipients. RI correlated with age, both in donors (r = 0.58, P < 0.001) and recipients (r = 0.39, P < 0.001). In recipients, 10 or more years younger than their donors (n = 24), an average decrease of 0.05 in RI compared to the donors' value was observed (P = 0.01). Heart rate, cold and warm ischaemia time and immunosuppressive medications had no influence on the recipient RI. In patients with delayed graft function, a significant increase in RI within 14 days was observed. However, the initial RI was not predictive of graft function. Conclusions. The transplanted kidney seems to be able to adjust its RI within a short time despite several potential harmful factors that can occur during the transplantatio

Risk factors for polyoma virus nephropathy

Background. Polyoma virus-associated nephropathy (PVN) is a common cause of renal transplant failure. The risk factors for the development of PVN have not yet been studied in large cohorts of patients for periods of 20 years. Methods. We collected clinical, renal biopsy and urinary cytology data from all patients with renal transplantations performed at the University Hospital of Basel from 1985 to 2005. All patients with a renal biopsy and urine cytology were included (n = 880). Renal transplants were divided into three groups, according to evidence of polyoma virus (PV) infection (decoy cells in the urine) and biopsy-proven PVN: Renal transplants without evidence of a PV infection (n = 751). Renal transplants with PV reactivation, e.g. decoy cell (DC) found by urinary cytology, but without PVN (n = 90). Renal transplants with PVN (n = 39). Results. The prevalence of biopsy-proven PVN in this cohort of patients was 3.3%. Immunosuppression with mycophenolate and/or tacrolimus, ATGAM, male gender of the recipient and a higher number of transplant rejection episodes were factors significantly associated with PVN development. Conclusions. The most important risk factors for the development of PVN are acute rejection and ATGAM used as induction therapy as well as tacrolimus and mycophenolate as maintenance therapy. Therefore, we conclude that patients with tacrolimus and mycophenolate maintenance therapy should be carefully monitored for the development of PV

Complications of retroperitoneoscopic living donor nephrectomy: single center experience after 164 cases

Objectives: Retroperitoneoscopic living donor nephrectomy (RLDN) is used by only a few centers worldwide. Similar to laparoscopic living donor nephrectomy it offers the donor rapid convalescence and excellent cosmetic results. However, concerns have been expressed over the safety of endoscopic living donor nephrectomy. Methods: We review the results of 164 consecutive RLDN from November 2001 to November 2007. Complications were classified into intra- and early postoperative. Results: Mean donor age was 53.4±10.7years (27-79). Left kidneys were harvested in 76% of cases. Mean operation time was 146±44min (55-270), and warm ischemia time 131±45s (50-280). In two patients (1.2%) conversion to open nephrectomy was necessary. The intraoperative complication rate was 3.0%. In the postoperative period we observed in 17.7% minor complications with no persisting impairments for the donor. The rate of major complications in the early postoperative period was 4.3%. Three patients (1.8%) necessitated revision, due to laceration of the external iliac artery in one patient and chyloretroperitoneum in two patients. Mean donor creatinine was 113.1±26.6mg/dl (63-201) on the first postoperative day, and 102.0±22.2mg/dl (68-159) on the fifth postoperative day. Conclusion: Retroperitoneoscopic living donor nephrectomy can be performed with acceptable intraoperative and early postoperative morbidity. Operation times and warm ischemia times are comparable to the open approac