Alginate encapsulant incorporating CXCL12 supports long-term allo- and xenoislet transplantation without systemic immune suppression.

Islet transplantation represents a potentially curative approach for individuals with Type I Diabetes. The requirement for systemic immune suppression to control immune-mediated rejection of transplanted islets and the limited human islet supply represent significant roadblocks to progress for this approach. Islet microencapsulation in alginate offers limited protection in the absence of systemic immunosuppression, but does not support long-term islet survival. The chemokine, CXCL12, can repel effector T cells while recruiting immune-suppressive regulatory T cells (Tregs) to an anatomic site while providing a prosurvival signal for beta-cells. We proposed that coating or encapsulating donor islets with CXCL12 would induce local immune-isolation and protect and support the function of an allo- or xenograft without systemic immune suppression. This study investigated the effect of alginate microcapsules incorporating CXCL12 on islet function. Islet transplantation was performed in murine models of insulin-dependent diabetes. Coating of islets with CXCL12 or microencapsulation of islets with alginate incorporating the chemokine, resulted in long-term allo- and xenoislet survival and function, as well as a selective increase in intragraft Tregs. These data support the use of CXCL12 as a coating or a component of an alginate encapsulant to induce sustained local immune-isolation for allo- or xenoislet transplantation without systemic immunosuppression.

Concomitance of IgA nephropathy and diabetic nephropathy in a kidney allograft: case report and review of the literature.

Whereas diabetic nephropathy is the most common cause of end-stage renal disease (ESRD), IgA nephropathy is the most common glomerulonephritis in the world. We report a case of a kidney transplant recipient whose native renal disease was presumptive diabetic nephropathy. Five years after transplantation, the patient developed proteinuria, hematuria, and allograft dysfunction. Transplant biopsy revealed IgA nephropathy superimposed on diabetic nephropathy.

An uncommon glomerular disease in an HIV patient: value of renal biopsy and review of the literature.

Renal disease is not uncommon in those infected with HIV. The most common manifestation of HIV in the kidney is HIV-associated nephropathy (HIVAN). Other HIV- and non-HIV-related causes have been described in the literature. Immunotactoid glomerulonephritis (ITG) is a rare disorder found in 0.06% of renal biopsies characterized by organized tubular immune complex deposits, observed more often in Caucasians. ITG tends to occur in an older age group and in some patients has been associated with a hemopoietic malignancy. In this report, we describe a case of ITG occurring in an HIV-positive, hepatitis C (HCV)- and hepatitis B (HBV)-negative female, who presented with microscopic hematuria and proteinuria. A percutaneous kidney biopsy showed diffuse membranous glomerulopathy, with mild mesangial proliferation and segmental sclerosing lesions containing mainly IgG, Kappa- and C3-positive deposits. Electron microscopy revealed diffuse subepithelial tubular deposits diagnostic of ITG. Out of 5 reported HIV-positive cases and ITG in the literature, 3 were HCV+, 2 were Caucasian and 3 were African-American (AA) without detectable hematologic malignancy. We report another case of ITG in an HCV- and HBV-negative, AA female.

Deceased donor kidney transplantation in elderly patients: is there a difference in outcomes?

INTRODUCTION: There is a paucity of data on long-term outcomes of older kidney recipients. Our aim was to compare the early and long-term outcomes of deceased donor kidney transplantation in patients aged >or=60 years with outcomes in younger recipients. MATERIALS AND METHODS: From 1998 to 2005, we performed 271 deceased donor kidney transplants. There were 76 recipients (28.1%) >60 years old. Older candidates were carefully selected based on their physiologic, cardiac, and performance status. Demographic data, including clinical characteristics, early complications, mortality, and patient and graft survival rates, were collected and analyzed. RESULTS: Older patients had comparable perioperative mortality and morbidity, incidence of delayed graft function (DGF), length of stay, and readmissions compared with younger patients. The rates of acute rejection and major infections were also comparable between the 2 study groups. Among older recipients, 25/76 (32.1%) patients received extended criteria donor kidneys compared with only 35/195 (17.9%) of younger patients (P < .001). Nevertheless, equivalent 1-, 3-, and 5-year allograft survival rates were observed in elderly and young patients; 91.5% versus, 92.5%, 78.5% versus 81.9%, and 75.6% versus 78.5%, respectively. Overall patient survival was also comparable in both groups. CONCLUSION: Kidney transplantation in appropriately selected elderly recipients provides equivalent outcomes compared with those observed in younger patients. These observations support the notion that older recipients should not lose access to deceased donor kidney transplantation in the effort to achieve a perceived gain in social utility.

Outcome of kidney transplantation using expanded criteria donors and donation after cardiac death kidneys: realities and costs.

Expanded criteria donors (ECDs) and donation after cardiac death (DCD) provide more kidneys in the donor pool. However, the financial impact and the long-term benefits of these kidneys have been questioned. From 1998 to 2005, we performed 271 deceased donor kidney transplants into adult recipients. There were 163 (60.1%) SCDs, 44 (16.2%) ECDs, 53 (19.6%) DCDs and 11 (4.1%) ECD/DCDs. The mean follow-up was 50 months. ECD and DCD kidneys had a significantly higher incidence of delayed graft function, longer time to reach serum creatinine below 3 (mg/dL), longer length of stay and more readmissions compared to SCDs. The hospital charge was also higher for ECD, ECD/DCD and DCD kidneys compared to SCDs, primarily due to the longer length of stay and increased requirement for dialysis (70,030 dollars, 72,438 dollars, 72,789 dollars and 47,462 dollars, respectively, p < 0.001). Early graft survival rates were comparable among all groups. However, after a mean follow-up of 50 months, graft survival was significantly less in the ECD group compared to other groups. Although our observations support the utilization of ECD and DCD kidneys, these transplants are associated with increased costs and resource utilization. Revised reimbursement guidelines will be required for centers that utilize these organs.

Noninvasive diagnosis of renal-allograft rejection by measurement of messenger RNA for perforin and granzyme B in urine.

BACKGROUND: Acute rejection is a serious and frequent complication of renal transplantation, and its diagnosis is contingent on the invasive procedure of allograft biopsy. A noninvasive diagnostic test for rejection could improve the outcome of transplantation. METHODS: We obtained 24 urine specimens from 22 renal-allograft recipients with a biopsy-confirmed episode of acute rejection and 127 samples from 63 recipients without evidence of acute rejection. RNA was isolated from the urinary cells. Messenger RNA (mRNA) encoding the cytotoxic proteins perforin and granzyme B and a constitutively expressed cyclophilin B gene were measured with the use of a competitive, quantitative polymerase chain reaction, and the level of expression was correlated with allograft status. RESULTS: The log-transformed mean (+/-SE) levels of perforin mRNA and granzyme B mRNA, which encode cytotoxic proteins, but not the levels of constitutively expressed cyclophiiin B mRNA, were higher in the urinary cells from the 22 patients with a biopsy-confirmed episode of acute rejection than in the 63 recipients without an episode of acute rejection (perforin, 1.4+/-0.3 vs. -0.6+/-0.2 fg per microgram of total RNA; P<0.001; and granzyme B, 1.2+/-0.3 vs. -0.9+/-0.2 fg per microgram of total RNA; P<0.001). Analysis involving the receiver-operating-characteristic curve demonstrated that acute rejection can be predicted with a sensitivity of 83 percent and a specificity of 83 percent with the use of a cutoff value of 0.9 fg of perforin mRNA per microgram of total RNA, and with a sensitivity of 79 percent and a specificity of 77 percent with the use of a cutoff value of 0.4 fg of granzyme B mRNA per microgram of total RNA. Sequential urine samples were obtained from 37 patients during the first nine days after transplantation; and measurements of the levels of mRNA that encoded cytotoxic proteins identified those in whom acute rejection developed. CONCLUSIONS: Measurement of mRNA encoding cytotoxic proteins in urinary cells offers a noninvasive means of diagnosing acute rejection of renal allografts.

Renin system activation and delayed function of the renal transplant.

Delayed graft function (DGF), defined as persistent renal failure that requires dialysis within the first week after kidney transplantation, occurs commonly after cadaveric renal transplantation (CRT). This has important implications for long-term outcome because the 1-year allograft survival rate is significantly reduced when DGF occurs. The mechanisms contributing to the development of DGF are not well established. However, several lines of evidence indicate that excess renin system activity, in both the cadaver kidney donor and recipient, contributes importantly to the pathogenesis of DGF. If this hypothesis can be verified in clinical studies, then pharmacologic agents that interrupt the renin-angiotensin system (eg, type 1 angiotensin II receptor blockade, angiotensin converting enzyme inhibition, and beta-adrenergic blockade) in the donor and recipient might significantly improve the outcome of cadaveric renal transplants.

The role of air plethysmography in monitoring results of venous surgery.

The development of an objective, noninvasive method to assess the hemodynamic effects of venous surgery has long been awaited. Previous methods used to evaluate the results of surgery for varicose veins and venous stasis ulceration have been limited in their quantitative assessment. Now, by use of air plethysmography (APG), we can accurately quantify the effectiveness of corrective venous surgery. Twenty-five extremities that had evidence of venous insufficiency were examined with use of APG before and after venous surgical procedures. Surgery was directed at specific sites of venous incompetence as defined by physical examination and high-resolution duplex imaging. Twenty-one extremities underwent ligation and stripping of the greater saphenous vein. In these patients, APG showed an improvement in venous reflux as demonstrated by a decrease in the venous filling index from 6.6 +/- 0.7 ml/sec to 1.8 +/- 0.3 ml/sec (p = 0.0001) and venous volume from 177.1 +/- 14.5 ml to 139.2 +/- 8.9 ml (p = 0.0008). In addition, these patients showed a mild improvement in calf muscle pump function as noted by an improvement in ejection fraction from 45.8 +/- 2.0% to 50.8% +/- 2.5% (p = 0.07). The residual volume fraction decreased from 45.0% +/- 3.4% to 42.0% +/- 3.7%, a difference that was not statistically significant (p = 0.4). Four extremities with grade III chronic venous insufficiency underwent popliteal vein valve transplantation with use of an autogenous axillary vein valve.(ABSTRACT TRUNCATED AT 250 WORDS)

Physiologic similarities between extremities with varicose veins and with chronic venous insufficiency utilizing air plethysmography.

Air plethysmography (APG) was used to measure maximal venous outflow rate (MVO), a test for proximal venous obstruction; venous volume; venous filling index, an estimate of valvular incompetence; ejection fraction (EF), a test of calf-muscle pump efficiency; and residual volume fraction (RVF), an estimate of ambulatory venous pressure. MVO was lower in patients with chronic venous insufficiency (CVI) than in those with varicose veins (VV), but the difference was small (p = 0.06). RVF was significantly greater in extremities with CVI when compared with those with VV (p less than 0.01). However, the degree of abnormality in venous volume, venous filling index, and EF was similar in CVI and VV extremities. In summary, although RVF tends to be higher in extremities with CVI when compared with those with VV, there is tremendous overlap between VV and CVI for each of the hemodynamic variables measured by APG. Therefore, the pathophysiology of CVI is likely to involve not only hemodynamic abnormalities but also other factors that have not yet been clearly identified.