Tibor Nadasdy

Treatment of C4D-positive acute humoral rejection with plasmapheresis and rabbit polyclonal antithymocyte globulin

Background. Alloantibody-mediated acute rejection is a major cause of renal allograft loss despite aggressive therapy. Patients with humoral rejection can be identified with high sensitivity and specificity by the presence of peritubular capillary C4d staining on renal biopsy and donor-specific anti-human leukocyte antigen antibodies. Standard therapy for acute humoral rejection (AHR) has been removal of donor-specific antibodies by plasmapheresis (PPH) in conjunction with intravenous immunoglobulin therapy. We describe a series of seven patients with C4d positive AHR who received combined therapy with PPH and polyclonal rabbit antithymocyte globulin (rATG). Methods. PPH (1.4 volume exchange) was initiated on diagnosis of AHR on an alternate day basis for a mean number of 6.8 treatments, in conjunction with rATG (0.75 mg/kg/day 5–10 days) until the serum creatinine returned to 120% of nadir. Results. The nadir posttreatment creatinine was significantly lower than pretreatment creatinine (1.0±1.2 vs. 2±1.4, P <0.007) with only one episode of graft loss. On follow-up there was no difference in renal allograft survival between the AHR group and the 60 patients without AHR who underwent transplantation during the same period. We describe the ability of rATG to induce apoptosis in vitro peripheral blood and activated B cells. Conclusion. Combination therapy using PPH and rATG is an effective means of reversing AHR in renal allografts.

Clinicopathologic correlates of prednisone treatment of human immunodeficiency virus-associated nephropathy

A 43-year-old man with rapidly evolving renal failure from biopsy-proven human immunodeficiency virus (HIV)-associated nephropathy (HIVAN) and superimposed thrombotic microangiopathic changes was treated with prednisone. His serum creatinine decreased from 7.5 to 3.9 mg/dL, and the 24-hour protein excretion decreased from 15.7 to 6.1 g over 6 to 8 weeks. As the prednisone was tapered, however, the creatinine began to increase, and a repeat biopsy was done to assist with therapeutic decisions. The major differences from the pretreatment biopsy were marked reductions in interstitial lymphocytes and macrophages and absence of thrombotic microangiopathic lesions. This is the first report comparing pretreatment and posttreatment renal biopsy specimens and the findings provide some insight into the means by which prednisone exerts its beneficial clinical effects acutely on this disease.

Chronic active myocarditis following acute Bartonella henselae infection (Cat Scratch Disease)

An association between Bartonella infection and myocardial inflammation has not been previously reported. We document a case of a healthy young man who developed chronic active myocarditis after infection with Bartonella henselae (cat scratch disease). He progressed to severe heart failure and underwent orthotopic heart transplantation. Bartonella henselae, therefore, should be included among the list of infectious agents associated with chronic active myocarditis.

Cholesterol embolization in renal allografts

Renal cholesterol embolization (RCE) in native kidneys has a dismal outcome and frequently leads to irreversible renal failure. RCE may rarely occur in renal allografts as well, particularly if the recipient or the donor has prominent atherosclerosis. The natural history of RCE in renal transplants is unknown. We have reviewed the surgical pathology files of The Johns Hopkins Hospital in the 14-year period between 1984 and early 1999 and found 7 RCE cases among 1500 renal transplant biopsies (0.47%). One of the seven cases had three biopsies showing cholesterol emboli, the first of which was a postreperfusion (immediate posttransplant) biopsy. The probable source of the cholesterol emboli was the recipient in six cases and the donor in one case. Five donors were cadaveric and two were living donors. Six biopsies were taken within the first 4 months posttransplant (four were postreperfusion biopsies). One recent patient had the inciting event of arteriography and stent placement 2 years posttransplant and is currently doing well. One kidney failed due to posttransplant lymphoproliferative disorder (PTLD), another kidney failed with complicating opportunistic infections, and the other five were functioning 2 to 6 years posttransplant. A literature review revealed additional 14 RCE cases in renal transplants. Combining our cases with those in the literature (21 cases), reveals that the origin of the RCE was probably the recipient in 11 cases (seven cadaveric, two living-related, and two unknown), and the donor in 10 cases (eight cadaveric and two unknown). Graft failure occurred in two of the 11 cases, where RCE was of probable recipient origin. Seven of the 10 kidneys, where the RCE was probably of donor origin, failed due to allograft dysfunction; one of them also developed superimposed rejection and cytomegalovirus infection. We conclude that if RCE is originating in the recipient, graft survival is usually good. In contrast, if RCE is of donor origin, graft dysfunction and subsequent graft loss are common. The reason for this difference may be the more extensive RCE developing in an atherosclerotic cadaveric donor during organ procurement or severe trauma leading to death.

Diffuse glomerular basement membrane lamellation in renal allografts from pediatric donors to adult recipients

The transplantation of kidneys from pediatric cadaveric donors into adult recipients is performed in many centers. However, some studies indicate that the outcome of such renal transplants may be inferior compared with that of adult donors, particularly if the donor is an infant. Morphologic studies of failed pediatric donor kidneys in adult recipients describe various degrees of segmental or global glomerular sclerosis. The authors have performed ultrastructural examinations on such transplants and have identified six cases with diffuse irregular lamellation of the glomerular basement membrane (GBM), a change that may develop as early as 10 weeks after transplantation. The age of all donors was < or =6 years; three were infants. The incidence of the lesion was 9% at our institution in renal transplant patients who received a graft from donors <10 years old. Diffuse GBM lamellation has not been found in renal transplants from adult donors. Light microscopy showed various degrees of diffuse mesangial expansion, usually with segmental glomerular sclerosis. The patients had severe proteinuria. While recurrent focal segmental glomerular sclerosis (FSGS) has to be excluded, such diffuse GBM lamellation is generally not seen in recurrent FSGS cases. The pathogenesis of the lesion is most likely related to hyperperfusion injury of small pediatric donor kidneys grafted into adult recipients.

Digital imaging of black and white photomicrographs: Impact of file size

The publication of black and white photomicrographs has a long tradition in pathology. High-resolution film and quality objectives have been the backbone of generating quality photomicrographs suitable for publication. However, the digital imaging revolution has changed the way we view and capture images. As the quality of image capture devices increases and as their price decreases, more and more investigators are using digital imaging, and the use of color digital imaging for teleconferencing, telediagnosis, and reproduction is now well established. The purpose of this study was to determine the file sizes needed to obtain publication-quality black and white images using digital imaging technology. In this study, four experts in renal pathology reviewed 70 black and white images of various file sizes obtained from specimens representing a variety of renal histopathology. Without knowledge of the file size, the four renal pathologists graded the degree of pixelation, and the overall diagnostic and publication quality of the images. In all cases, digital imaging was capable of obtaining publication quality images equal to those achieved using film. The file size needed to achieve publication quality black and white images depended on magnification, with lower magnification images requiring larger file sizes.