Rosemary Ouseph

Recurrent and de novo glomerular disease after renal transplantation : A report from renal allograft disease registry (RADR)

INTRODUCTION Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP.

Models and methods for analyzing DCE‐MRI: A review

PURPOSE To present a review of most commonly used techniques to analyze dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), discusses their strengths and weaknesses, and outlines recent clinical applications of findings from these approaches. METHODS DCE-MRI allows for noninvasive quantitative analysis of contrast agent (CA) transient in soft tissues. Thus, it is an important and well-established tool to reveal microvasculature and perfusion in various clinical applications. In the last three decades, a host of nonparametric and parametric models and methods have been developed in order to quantify the CAs perfusion into tissue and estimate perfusion-related parameters (indexes) from signal- or concentration-time curves. These indexes are widely used in various clinical applications for the detection, characterization, and therapy monitoring of different diseases. RESULTS Promising theoretical findings and experimental results for the reviewed models and techniques in a variety of clinical applications suggest that DCE-MRI is a clinically relevant imaging modality, which can be used for early diagnosis of different diseases, such as breast and prostate cancer, renal rejection, and liver tumors. CONCLUSIONS Both nonparametric and parametric approaches for DCE-MRI analysis possess the ability to quantify tissue perfusion.

Anticoagulation for Intermittent Hemodialysis

Hemodialysis is only possible on a routine basis if the tendency for blood to clot when in contact with foreign surfaces is inhibited. Early attempts at extracorporeal circulation used hirudin, extracted from leaches, to prevent coagulation (1, 2). These hirudin preparations appear to have had appreciable toxic side effects and it was not until heparin was adopted as an anticoagulant in the late 1920s that the problem of preventing clotting was removed as a major impediment to the development of hemodialysis (1, 2). Heparin has remained the drug of choice for preventing clotting during hemodialysis; it is relatively inexpensive and most hemodialysis machines are equipped so that heparin can be given with ease. However, an informal survey of chronic hemodialysis units shows no uniform approach to its dosing, in spite of the demonstration that control of anticoagulation can lead to improvements in urea clearance (3) and in dialyzer reuse (4). This article reviews the use of systemic heparinization for anticoagulation in hemodialysis and briefly describes the potential alternatives.

Effect of increasing dialysate flow rate on diffusive mass transfer of urea, phosphate and β2-microglobulin during clinical haemodialysis

Background. Diffusive clearance depends on blood and dialysate flow rates and the overall mass transfer area coefficient (KoA) of the dialyzer. Although KoA should be constant for a given dialyzer, urea KoA has been reported to vary with dialysate flow rate possibly because of improvements in flow distribution. This study examined the dependence of KoA for urea, phosphate and β2-microglobulin on dialysate flow rate in dialyzers containing undulating fibers to promote flow distribution and two different fiber packing densities. Methods. Twelve stable haemodialysis patients underwent dialysis with four different dialyzers, each used with a blood flow rate of 400 mL/min and dialysate flow rates of 350, 500 and 800 mL/min. Clearances of urea, phosphate and β2-microglobulin were measured and KoA values calculated. Results. Clearances of urea and phosphate, but not β2-microglobulin, increased significantly with increasing dialysate flow rate. However, increasing dialysate flow rate had no significant effect on KoA or Ko for any of the three solutes examined, although Ko for urea and phosphate increased significantly as the average flow velocity in the dialysate compartment increased. Conclusions. For dialyzers with features that promote good dialysate flow distribution, increasing dialysate flow rate beyond 600 mL/min at a blood flow rate of 400 mL/min is likely to have only a modest impact on dialyzer performance, limited to the theoretical increase predicted for a constant KoA.

Maintaining blood compartment volume in dialyzers reprocessed with peracetic acid maintains Kt/V but not β2-microglobulin removal

A dialyzer is reused if its blood compartment volume is 80% of its initial value, a condition believed to ensure that the urea clearance remains at 90% of its initial value. This criterion was developed for dialyzers containing low permeability cellulose membranes reprocessed with formaldehyde. We tested the hypothesis that the criterion is also valid for more permeable membranes when dialyzers are reprocessed with peracetic acid/hydrogen peroxide. Kt/V for urea and reduction in beta2-microglobulin concentration were measured for up to 15 uses in dialyzers containing polysulfone or cellulose membranes. Kt/V for urea did not change for either dialyzer provided blood compartment volumes remained 80% of their initial value. The reduction in plasma beta2-microglobulin concentration from predialysis to postdialysis was 30% for the first use of the dialyzer containing polysulfone membranes, but decreased significantly (P = 0.042) following reuse to 12% for the tenth use. For the dialyzers containing cellulose membranes, the reduction in plasma beta2-microglobulin concentration was 18% for the first use and decreased to 12% by the twelfth use; however, this change was not significant. We conclude that removal of urea is maintained during reuse with peracetic acid/hydrogen peroxide provided the blood compartment volume remains 80% of its initial value. However, removal of beta2-microglobulin may not be maintained, even though blood compartment volumes remain at 80% of their initial value.

3d kidney segmentation from CT images using a level set approach guided by a novel stochastic speed function

Kidney segmentation is a key step in developing any noninvasive computer-aided diagnosis (CAD) system for early detection of acute renal rejection. This paper describes a new 3-D segmentation approach for the kidney from computed tomography (CT) images. The kidney borders are segmented from the surrounding abdominal tissues with a geometric deformable model guided by a special stochastic speed relationship. The latter accounts for a shape prior and appearance features in terms of voxel-wise image intensities and their pair-wise spatial interactions integrated into a two-level joint Markov-Gibbs random field (MGRF) model of the kidney and its background. The segmentation approach was evaluated on 21 CT data sets with available manual expert segmentation. The performance evaluation based on the receiver operating characteristic (ROC) and Dice similarity coefficient (DSC) between manually drawn and automatically segmented contours confirm the robustness and accuracy of the proposed segmentation approach.

Review of the use of hepatitis B core antibody-positive kidney donors.

This article reviews the risks of transplanting hepatitis B core antibody (anti-HBc)-positive (+) kidneys and strategies to minimize the risks to the recipient. In the United States, there is a shortage of kidneys available for transplantation. Presently, 4% of kidneys transplanted are anti-HBc (+). In published retrospective studies, the serologic conversion rate for recipients of anti-HBc (+) kidneys varied between 0% and 27%; and the development of elevated hepatic transaminases varied between 0% and 26%. Only one published article had a trend toward increased risk of graft loss. Other published studies had no significant difference in graft or patient survival. Factors that influence the risk of transmission include hepatitis B viral load, vaccination, and antiviral therapy. If the donor is anti-HBc (+) and hepatitis B DNA negative, the risk of transmission is negligible; unfortunately, this information may not be available at the time of transplant. Vaccinated recipients with a protective hepatitis B surface antibody of at least 10 mIU/mL had a 4% conversion rate compared with 10% in recipients with antibody levels not exceeding 10 mIU/mL. Both hepatitis B immunoglobulin and lamivudine have been used in recipients of anti-HBc (+) kidneys to decrease seroconversion with success. The data do support the use of anti-HBc (+) kidneys if precautions are taken. The recipients should be informed of the risk, should be vaccinated with an adequate response, and should have surveillance serologies performed.

Dialysate flow rate and delivered Kt/Vurea for dialyzers with enhanced dialysate flow distribution.

BACKGROUND AND OBJECTIVES Previous in vitro and clinical studies showed that the urea mass transfer-area coefficient (K(o)A) increased with increasing dialysate flow rate. This observation led to increased dialysate flow rates in an attempt to maximize the delivered dose of dialysis (Kt/V(urea)). Recently, we showed that urea K(o)A was independent of dialysate flow rate in the range 500 to 800 ml/min for dialyzers incorporating features to enhance dialysate flow distribution, suggesting that increasing the dialysate flow rate with such dialyzers would not significantly increase delivered Kt/V(urea). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We performed a multi-center randomized clinical trial to compare delivered Kt/V(urea) at dialysate flow rates of 600 and 800 ml/min in 42 patients. All other aspects of the dialysis prescription, including treatment time, blood flow rate, and dialyzer, were kept constant for a given patient. Delivered single-pool and equilibrated Kt/V(urea) were calculated from pre- and postdialysis plasma urea concentrations, and ionic Kt/V was determined from serial measurements of ionic dialysance made throughout each treatment. RESULTS Delivered Kt/V(urea) differed between centers; however, the difference in Kt/V(urea) between dialysate flow rates of 800 and 600 ml/min was NS by any measure (95% confidence intervals of -0.064 to 0.024 for single-pool Kt/V(urea), -0.051 to 0.023 for equilibrated Kt/V(urea), and -0.029 to 0.099 for ionic Kt/V). CONCLUSIONS These data suggest that increasing the dialysate flow rate beyond 600 ml/min for these dialyzers offers no benefit in terms of delivered Kt/V(urea).

Shape-Appearance Guided Level-Set Deformable Model for Image Segmentation

A new speed function to guide evolution of a level-set based active contour is proposed for segmenting an object from its background in a given image. The guidance accounts for a learned spatially variant statistical shape prior, 1st-order visual appearance descriptors of the contour interior and exterior (associated with the object and background, respectively), and a spatially invariant 2nd-order homogeneity descriptor. The shape prior is learned from a subset of co-aligned training images. The visual appearances are described with marginal gray level distributions obtained by separating their mixture over the image. The evolving contour interior is modeled by a 2nd-order translation and rotation invariant Markov-Gibbs random field of object/background labels with analytically estimated potentials. Experiments with kidney CT images confirm robustness and accuracy of the proposed approach.

Patent foramen ovale presenting as refractory hypoxemia after heart transplantation

Hypoxemia can be an early life-threatening complication of orthotopic heart transplantation. Commonly, hypoxemia after orthotopic heart transplantation is due to pulmonary hypertension or pulmonary complications. Rarely, structural defects either in the donor or recipient heart can lead to life-threatening hypoxemia. This case illustrates hypoxemia after orthotopic heart transplantation caused by the development of a right-to-left shunt through a patent foramen ovale in the recipient which had preoperatively been hemodynamically insignificant. The refractory hypoxemia required emergency surgical correction of the patent foramen ovale within the first postoperative week. In addition, this case illustrates the unique application of different methods of echocardiograms providing noninvasive diagnosis of structural defects in orthotopic heart transplantation.