Glomerular endothelial vesicles in a renal allograft: an unusual pattern of immunoglobulin deposition in a patient with biclonal gammopathy of unknown significance.

Paraproteins have varied effects on the kidney on the basis of molecular structure, concentration, and renal function. Prototypical patterns include myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, and amyloid, among others. We report a 69-year-old man with end-stage diabetic nephropathy and biclonal gammopathy of unknown significance. Serum monoclonal immunoglobulin G (IgG)-κ and urine monoclonal free λ light chains were identified during workup for nephrotic syndrome. A native renal biopsy demonstrated diabetic nephropathy, without indication of paraprotein-related pathology. After transplantation, a surveillance biopsy showed endothelialitis (type 2 rejection) and abundant eosinophilic droplets, nearly occluding glomerular capillary loops. Electron microscopy localized tightly packed electron-dense vesicles in glomerular endothelial cells. Immunofluorescence studies revealed IgG-κ-dominant endothelial staining, along with λ monotypic protein resorption droplets in tubules. Two additional biopsies within the following year showed this same paraprotein distribution, with some increase in mesangial sclerosis. Two years after transplant the patient remains asymptomatic with normal creatinine levels. Literature review yields rare cases of immunoglobulin crystalline deposits in multiple glomerular cell types, rarely including endothelial cells; however, this appears to be the first report of monoclonal immunoglobulin vesicles localized solely to endothelial cells. As these vesicles were not seen in the native kidney biopsy, we hypothesize an interaction of alloimmune-mediated endothelial injury and the physiochemical properties of the IgG-κ paraprotein. In addition, this case illustrates simultaneous different patterns of accumulation of monoclonal immunoglobulin and light chain components in this unique patient with biclonal gammopathy of unknown significance.

Surveillance and modification of immunosuppression minimizes BK virus nephropathy.

BACKGROUND/AIMS: Infection of a transplanted kidney with the polyomavirus, BK, is associated with poor allograft survival. METHODS: In an attempt to prevent this transplant complication, we studied 144 consecutive transplant recipients for the presence of BK infection with plasma and urine PCR testing at 1, 2, 3, 6 and 12 months. Viruria alone was followed by serial studies. If plasma PCR became positive at >2.6 log copies, mycophenolate was reduced until there was no detectable plasma viral load. RESULTS: Urine PCR was positive in 34 (24%), while plasma PCR turned positive in 22 cases (15%). No patients developed viremia with <6.8 log copies in the urine. Viremia resolved within 3 months or less in 20 of 22 patients after reduction of immunosuppression. Surveillance biopsies at 2 and 6 months revealed no BK nephropathy. Eight patients had acute rejection during reduced immunosuppression; however, all of these reversed with pulse steroids. Patient and graft survival at 1 year was 99 and 98%, respectively. Use of the cell-mediated immunity assay (ImmuKnow, Columbia, Md., USA) was not useful in identifying infected patients. CONCLUSION: Active surveillance for BK virus by urine/plasma PCR with prompt reduction in immunosuppression can prevent BK nephropathy.

Severe prolonged tacrolimus overdose with minimal consequences.

A 59-year-old man inadvertently received a 10-fold increase in his twice-daily oral dose of tacrolimus 1 mg that resulted in trough blood levels above 90 ng/ml for over a week. The patient had end-stage renal disease secondary to diabetes mellitus and had received a kidney transplant from his daughter 3 months earlier. Despite the numerous adverse effects commonly reported with tacrolimus, such as mild nephrotoxicity, nausea, tremors, and elevated liver enzyme levels, our patient's acute but prolonged overdose resulted in minimal signs and symptoms of toxicity. Nevertheless, education regarding the importance of accurate dosing, close monitoring, potential drug interactions, and the various capsule colors should be provided to all patients who receive tacrolimus, as well as their physicians, nurses, and pharmacists, in order to prevent as many errors as possible.

Creatinine reduction ratio and 24-hour creatinine excretion on posttransplant day two: simple and objective tools to define graft function.

To devise objective criteria for early diagnosis of delayed graft function (DGF), 59 adult living donor kidney transplants with immediate graft function (IGF) and 51 cadaveric kidney transplants were investigated for creatinine reduction ratio (CRR2) from posttransplant day 1 to day 2 and 24-h urine creatinine excretion (UC2) on day 2. The mean CRR2 in living donor transplants was 53% (SD +/- 11); the distribution of CRR2 was gaussian, and all of them had UC2 >1000 mg. Criteria for DGF were developed on the basis of living donor transplant: CRR2 < or =30% (2SD below 53%) +/- UC2 < or =1000 mg. Overall, 24 cadaver transplant recipients (47%) developed DGF (CRR2 < or =30%); 13 patients (25%) had mild DGF (UC2 >1000 mg), and the remaining 11 (22%) had severe DGF (UC2 < or =1000 mg). All the patients with severe DGF had a measured creatinine clearance <25 ml/min on day 7, and 8 of 11 were dialyzed within the first week of transplantation. Patients with IGF and mild DGF had a creatinine clearance of > or =25 ml/min on or before day 7, and none of them were dialyzed. Calcineurin inhibitors were avoided or delayed in five patients with mild DGF and all patients with severe DGF. In conclusion, diagnosing DGF within 48-h after transplantation is simple and may be valuable in the management of these patients.

Infectious disease prophylaxis in renal transplant patients: a survey of US transplant centers.

Definitive approaches to most infectious diseases following renal transplantation have not been established, leading to different approaches at different transplant centers. To study the extent of these differences, we conducted a survey of the practices surrounding specific infectious diseases at US renal transplant centers. A survey containing 103 questions covering viral, bacterial, mycobacterial and protozoal infections was developed. Surveys were sent to program directors at all U.S. renal transplant centers. Responses were received from 147 of 245 (60%) transplant centers and were proportionately represented all centers with respect to program size and geographical location. Pre-transplant donor and recipient screening for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cytomegalovirus (CMV) is uniform, but great discrepancy exists in the testing for other agents. HCV seropositive donors are used in 49% of centers. HIV seropositivity remains a contraindication to transplantation, although 13% of centers indicated they have experience with such patients. Post-transplant, there is wide variety in approach to CMV and Pneumocystis carinii (PCP) prophylaxis. Similarly divergent practices affect post-transplant vaccinations, with 54% of centers routinely vaccinating all patients according to customary guidelines in non-transplant populations. In contrast, 22% of centers indicated they do not recommend vaccination in any patients. We believe an appreciation of the differences in approaches to post-transplant infectious complications may encourage individual centers to analyse the results of their own practices. Such analysis may assist in the design of studies to answer widespread and important questions regarding the care of patients following renal transplantation.