Outcome of desensitization in human leukocyte antigen- and ABO-incompatible living donor kidney transplantation: a single-center experience in more than 100 patients.

BACKGROUND: Antibody-mediated rejection (AMR) and inferior graft outcome remain the 2 most important obstacles to successful kidney transplantation in human leukocyte antigen (HLA)- and ABO-incompatible recipients. We report a single-center experience in the outcome of desensitized living donor HLA- and ABO-incompatible kidney transplantation. METHODS: Since 2007 we included 2 groups in our desensitization program. HLA-incompatible living donor kidney transplant candidates displaying donor-specific antibodies (DSA) with or without a positive T-cell and/or B-cell flow crossmatch (FCXM). Second, those displaying DSA with positive T-cell immunoglobulin (Ig)G AHG CDC CXM with a titer of ≤1:8, as well as all ABO-incompatible living donor kidney transplant candidates with an IgM isoagglutinin titer ≤ 256. They were risk stratified for AMR and underwent individualized desensitization protocol: ABO-incompatible and HLA-incompatible candidates with either positive AHG CDC CXM or positive T and/or B IgG flow CXM with repeat HLA mismatch from a previous transplantation were deemed to be high risk and received a single dose of Rituximab, therapeutic plasma exchange and high-dose intravenous immunoglobulin (IVIG) (2 g/kg). HLA-incompatible candidates with negative CDC but positive T and/or B IgG FCXM were deemed intermediate risk, receiving rituximab and high-dose IVIG. Those with positive DSA but negative flow and CDC CXM were deemed low risk, receiving low-dose IVIG (1 g/kg). All patients received induction with thymoglobulin and were maintained on a tacrolimus-based immunosuppressive regimen. RESULTS: Among 124 incompatible recipients, 85 received HLA-incompatible and 39 ABO-incompatible living donor kidney transplantations after desensitization. Risk stratification for HLA-incompatible transplants revealed 61 high-risk, 42 intermediate-risk, and 21 low-risk cases. Ninety-nine (80%) were primary transplants. At a median follow-up of 23 (range 1-53) months, patient survival was 98% and death censored graft survival 96%. Mean serum creatinine was 84 µmol/L (range 41-169). Acute cellular rejection was observed in 15 (12%) and AMR in 5 (4%) patients. All rejection episodes responded to treatment except 1 AMR in an ABO-incompatible transplant that led to graft failure. CONCLUSION: Our risk stratification for desensitization strategy achieved a low incidence of AMR among HLA- and ABO-incompatible kidney transplant recipients. Their 2-year data appear to be comparable to HLA- and ABO-compatible transplantations.

Bortezomib as an adjuvant to conventional therapy in the treatment of antibody mediated rejection (AMR): the full spectrum.

Antibody-mediated rejection (AMR) is a well-known complication of kidney transplantation. Its incidence is higher in HLA and ABO incompatible transplant recipients and in patients who develop de novo HLA antibodies. Different clinical and histological phenotypes of HLA-related AMR have been described with variable responses to conventional AMR treatment (Plasmapheresis, IVIG, thymoglobulin (ATG), and anti-CD20 antibodies). Regardless of the phenotype, once the HLA primed B cells have differentiated into antibody producing long-lived plasma cells, they become less vulnerable to conventional AMR treatment. Bortezomib (Velcade) is a proteasome inhibitor approved by the FDA for the treatment of multiple myeloma. It targets mature plasma cells, and hence it is intriguing to study its role in the suppression of long-lived plasma cells. Several previous reports have suggested effectiveness of Bortezomib in the treatment of AMR. We report our experience with Bortezomib as an adjuvant to conventional therapy in five distinct phenotypes of AMR: early acute AMR in the context of desensitization; subclinical acute AMR in the context of desensitization; late acute AMR due to de novo HLA antibody; late ACR and acute AMR due to de novo HLA antibody and chronic AMR due to de novo HLA antibody.

Renal involvement in Behçet's disease: review of 9 cases.

We describe clinical data on 9 patients with Behçet's disease with renal involvement (8 males, one female) and results of kidney biopsies in 4 patients. Renal involvement occurred in 9 of 120 patients (7.5%) followed at our center. Proteinuria was present in 8 patients (6 with quantitative 24 h urine protein with a range of 0.32-3.11 g/day, mean 1.7 g/day); hematuria occurred in one patient. Impaired renal function was encountered in 2 patients at presentation and in another patient at a later date. Major vascular involvement (major venous and/or arterial thrombosis) was present in 4 patients and sagittal sinus thrombosis in another patient. Measurement of complement C3, C4, and CH50 and immunologic tests for anticardiolipin, antineutrophil cytoplasmic, and antistreptococcal antibodies did not indicate a clear association with renal involvement. Kidney biopsies were performed in 4 patients. Mesangial proliferative changes were observed in 3 patients and evidence of immune complex deposition by immunofluorescence and electron microscopic examination was present in 2 patients. Amyloidosis was present in one patient who had vascular involvement and presented with nephrotic range proteinuria.

Simultaneous development of Kaposi's sarcoma and lymphoma in a renal transplant recipient.

Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma are frequent complications of renal transplantation that usually occur as separate entities. We describe a young woman who simultaneously developed Kaposi's sarcoma and lymphoma after kidney transplantation. Immunosuppression consisted of cyclosporine and prednisone with normal serum creatinine. Fifteen months after transplantation, she developed Kaposi's sarcoma skin lesions, generalized lymphadenopathy, and ascites. A lymph node biopsy showed both Kaposi's sarcoma and lymphoma in the same tissue specimen with Epstein-Barr viral genomes within the tumor cells. Graft function remained normal. Cyclosporine was discontinued, and treatment with acyclovir was started, but the patient's condition rapidly deteriorated, and she died. This is the first case in which both Kaposi's sarcoma and lymphoma were present in the same biopsy specimen. After renal transplantation, more than one tumor can develop either simultaneously or in succession.

Renal artery stenosis in renal transplantation presentation and management.

A review of the angioplasty records between 1990 and 1995 at the King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia revealed ten cases of transplant renal artery stenosis (RAS). The diagnosis in these cases was confirmed by renal angiography and all were treated by angioplasty. All study patients presented with uncontrolled hypertension in spite of multiple medications; eight had renal functional impairment and two patients had recurrent unexplained pulmonary edema in addition. Six patients had undergone end-to-end anastomosis, while four had end-to-side anastomosis of the artery during transplantation. Four had cadaveric renal transplants and six had living donor renal transplants. Eight of these patients responded well to angioplasty with marked improvement in their renal function and reduction in the number of anti-hypertensive medications. In one patient, it was not possible to pass the catheter through the stenosis and the patient underwent surgical reconstruction, while in another patient there were multiple stenotic lesions involving the external iliac and the transplant renal arteries suggesting atherosclerotic changes. We conclude that renal artery stenosis should be suspected in patients after renal transplant if they have uncontrolled or worsening hypertension, unexplained renal impairment or presentation with unexplained recurrent pulmonary edema. Renal angiography should be considered as part of the investigation of hypertension in renal transplant patients, and if the RAS is confirmed, angioplasty should be the procedure of choice.

Hepatitis C virus infection in hemodialysis patients: comparison of two new hepatitis C antibody assays with a second-generation assay.

The performance of two new hepatitis C virus antibody (anti-HCV) assays (a third-generation immunoglobulin (Ig)G recombinant immunoblot assay (RIBA 3.0) and hepatitis C virus core IgM (HCV IgM) in the prediction of hepatitis C viremia in hemodialysis patients was compared with that of a second-generation IgG recombinant immunoblot assay (RIBA 2.0). Forty-three patients on maintenance hemodialysis were studied. Aliquots of sera were tested prospectively for anti-HCV by RIBA 2.0, RIBA 3.0, and HCV IgM and for HCV RNA by polymerase chain reaction. Thirty-eight patients were HCV RNA positive. Among those, 7 (18%) were HCV IgM positive, 22 (58%) were RIBA 2.0 positive, and 29 (76%) were RIBA 3.0 positive. All but one viremic patients detected by HCV IgM were also detected by RIBA 2.0 and RIBA 3.0. All viremic patients detected by RIBA 2.0 were also detected by RIBA 3.0. RIBA 3.0 was more sensitive than RIBA 2.0 and HCV IgM in the detection of viremic patients (P = 0.0156 and < 0.0001, respectively). The positive predictive value for HCV IgM was 100% as compared with 96 and 97% for RIBA 2.0 and RIBA 3.0, respectively. The negative predictive value for RIBA 3.0 was 36% as compared with 24 and 14% for RIBA 2.0 and HCV IgM, respectively. At 6-months follow-up of the eight viremic patients without a detectable IgM or IgG anti-HCV response, all patients remained RIBA 2.0 nonreactive, one became RIBA 3.0 indeterminate, and one became HCV IgM positive. These data suggest that HCV IgM has poor sensitivity in the detection of hepatitis C viremia and RIBA 3.0 improves the sensitivity of IgG anti-HCV assays in the early detection of hepatitis C viremia in hemodialysis patients.

Sneddon's syndrome: a systemic arterio-occlusive disorder.

We describe a case of Sneddon's syndrome in a young woman with malignant hypertension and renal impairment. Kidney biopsy demonstrated intimal proliferation of small and medium-sized renal arteries similar to that seen in cutaneous arteries of patients with this syndrome. Ultrastructural examination showed the proliferated intima to be composed of smooth muscle fibers, fibroblasts, monocytes, and extensive deposition of dense granular and light-staining amorphous materials. Our findings support the proposition that Sneddon's syndrome may not be simply a neurocutaneous vascular disorder as originally described, but rather a systemic arterioocclusive disorder with a variable clinical expression.

New insights into hepatitis C virus infection of hemodialysis patients: the implications.

The authors compared the diagnostic performance of a second-generation recombinant immunoblot assay (RIBA) (RIBA HCV 2.0 SIA) and the recently introduced third-generation RIBA (RIBA HCV 3.0 SIA) with that of hepatitis C virus (HCV) RNA by the polymerase chain reaction (PCR) in 55 patients on chronic hemodialysis. Compared with HCV RNA by PCR, RIBA 3.0 increased the sensitivity of HCV detection to 72% as compared with 56% of RIBA 2.0. Both assays underestimated the prevalence of HCV infection as determined by PCR. However, RIBA HCV 3.0 outperformed RIBA HCV 2.0, detecting all of the RIBA 2.0-positive patients plus an additional eight (8 of 22 RIBA 2.0 negative; confidence interval [CI] = [17.2%, 59.3%]). Forty-three of 51 patients with positive RIBA 3.0 or positive HCV RNA by PCR underwent a liver biopsy. Thirty (70%) had chronic hepatitis (three with cirrhosis), 10 (23%) had nonspecific changes, and three (7%) had normal liver histology. Thirty of 37 patients (81%) with hepatitis C viremia and positive anti-HCV had chronic hepatitis, whereas none of the viremic patients with negative anti-HCV had chronic hepatitis. Among the reactive antigens on RIBA 3.0, c33c was found to be most predictive of chronic hepatitis (P = 0.0002). Detection of HCV RNA continues to be the method of choice in the early phase of HCV infection. In places where a validated HCV RNA assay is not available, RIBA HCV 3.0 (soon to be commercially available) is a better alternative. Early detection of HCV infection and the implementation of an isolation strategy might be important in preventing the spread of HCV infection among hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Impact of hepatitis C virus infection on kidney transplant outcome.

One hundred and forty kidney transplant recipients were evaluated to study the impact of hepatitis C virus (HCV) infection on patient and graft outcome. There .were 98 males arid 42 females with a mean age of 32.1 +/- 13 years. The duration of follow-up ranged from 6-60 months with a mean period of 27.8 +/- 18.2 months. Seventy-four (53%) patients had received cadaveric kidneys while 66 (47%) received living donor grafts. Anti-HCV reactivity was tested using second generation enzyme-linked immunosorbent assay and positivity was confirmed by recombinant immunoblot assay. HCV infection was diagnosed in 29 cases (20.7%) while HBsAg was found in nine (6.4%) and concomitant anti-HCV and HBsAg positivity was observed in two patients (1.4%). Seventeen of 29 (58.6%) patients with anti-HCV reactivity showed elevated ALT levels as against 17 of 111 (17.3%) anti-HCV non-reactive patients (P< 0.001). There was no association between the sex of the patient, source of the graft, and anti-HCV reactivity. Serum creatinine values were higher in the anti-HCV positive group, but this did not rank to statistical significance. We observed a significantly higher graft loss among the anti-HCV reactive group (27.6% versus 1.8%, P< 0.003). Thirteen anti-HCV reactive patients were subjected to 18 liver biopsies; the commonest lesion observed was chronic active hepatitis, which was progressive in two patients subjected to re-biopsy. We conclude that HCV infection is a serious health problem among kidney transplant recipients and it significantly affects the graft outcome.

Hepatitis C Virus Infection in a Hemodialysis and Kidney Transplant Patient: An Eight Year Follow-up Report.

We report our experience in the management of a hemodialysis (HD) patient who acquired hepatitis C virus (HCV) infection while on dialysis, and subsequently received a kidney transplant. The potential role of alpha-interferon in the management of HCV infection is discussed, as well as the potential for azathioprine to perpetuate HCV induced liver disease following kidney transplantation. The management of this patient summarizes our standard practice for the management of HCV infection during HD and following kidney transplantation.

Kidney transplantations at King Faisal Specialist Hospital and Research Centre.

During the five year period from 1987G to 1991G, 161 kidney transplantations were performed at King Faisal Specialist Hospital and Research Centre (KFSH&RC); 79 from cadaveric donors (CD) and 82 from living related donors (LRD). All cadaveric kidneys except one were harvested within Saudi Arabia and 67% were from Saudi nationals. The immunosuppresive protocol was a triple drug regimen comprising cyclosporin-A (CyA), azathioprine (Aza), and prednisone. The actuarial graft survival rates at one and three years were 85% and 76% for the cadaveric donor transplants and 96% and 91%, respectively for the living related donor transplants (P<0.01). The corresponding patient survival rates for cadaveric donor transplants (CDTxs) were 97% and 94% and for the living related donor transplants (LRDTxs), 99% and 97% (NS). These results compare well with the best results in the Western world. The most serious surgical complications were vascular thromboses (five cases) and infections of the arterial anastomosis line with bleeding (two cases), all leading to loss of the cadaveric graft. The most common causes of death were virus infection, varicella, cytomegalovirus, and hepatitis B and C. The organ donation rate, from cadaveric donors as well as living related donors, is stil low in Saudi Arabia. Lack of organs is the main obstacle to an expansion of this promising transplantation activity. Continuous education of the multinational medical profession as well as the lay population is necessary to improve the situation.