Acute transplant glomerulopathy is associated with antibody-mediated rejection and poor graft outcome.

Transplant glomerulopathy (TG) is traditionally considered to be a chronic entity. However, in our practice we observed patients who presented with features of TG as early as 14 days posttransplantation. We investigated the clinicopathological features of these cases. During a 4-year period, all patients with acute rejection were identified. Charts were reviewed to identify patients with antibody-mediated rejection and biopsy features of TG within 6 months posttransplantation. Three patients met the above-mentioned criteria. All of them had diffuse margination of inflammatory cells in peritubular capillaries in the setting of acute renal failure or delayed graft function. Monocyte (CD68-positive) margination in peritubular capillaries was a common feature. All 3 patients had donor-specific antibodies and features suggestive of antibody-mediated rejection. C4d stain in peritubular capillaries was focal and mild or absent in serial biopsies. Occlusive endothelial swelling of glomerular capillary loops (endotheliosis) preceded TG. None of the patients had evidence for other causes of similar glomerular changes in a transplant, such as calcineurin inhibitor toxicity, ischemia, hepatitis C, or immune complex glomerulonephritis. They did not have other biopsy features of chronicity when TG appeared and as it progressed. TG can occur as an acute phenomenon. We propose that endotheliosis is a more accurate and specific precursor of TG than mere glomerulitis. These cases of acute TG may represent a form of antibody-mediated rejection associated with proteinuria and poor response to treatment.

Late acute kidney transplant rejection: clinicopathological correlates and response to corticosteroid therapy.

Acute rejection is a major cause of kidney allograft dysfunction. It is important to distinguish between cellular and antibody-mediated rejection to guide the treatment strategy. The management of acute antibody-mediated rejection includes aggressive therapy with plasmapheresis and intravenous immunoglobulin. C4d staining of peritubular capillaries has emerged as a valuable tool in identifying antibody-mediated rejection. Late acute rejection has a worse prognosis than early acute rejection. The clinical and pathological features of late acute kidney allograft rejection are not fully understood. We studied the clinicopathological correlates of late acute rejection in our patient population. During an 8-year period, all patients who had late acute rejection (6 months posttransplant) were identified. Patients with severe chronic changes and transplant glomerulopathy were excluded. Patients were divided into C4d+ and C4d- groups [corrected]. Histopathological features and treatment response were evaluated. Nine patients met inclusion criteria (4 C4d+, 5 C4d-). Maintenance therapy consisted of mycophenolate mofetil, calcineurin inhibitors, and low-dose prednisone. All patients received intravenous methlyprednisolone or high-dose oral prednisone as antirejection therapy. Seventy-five percent of patients in the C4d+ group and 80% of patients in the C4d- group had a clinical response to antirejection therapy. The majority of C4d+ patients with late acute rejection who were treated with corticosteroids alone responded to treatment. The study raises the possibility that a subset of C4d+ patients with acute rejection who do not have severe chronic changes might respond to corticosteroid therapy alone.

Unrecognized acute phosphate nephropathy in a kidney donor with consequent poor allograft outcome.

Acute phosphate nephropathy following a large phosphate load is a potentially irreversible cause of kidney failure. Here, we report on the unfavorable graft outcome in two recipients of deceased donor kidneys from a donor who had evolving acute phosphate nephropathy at the time of organ procurement. The donor, a 30-year-old with cerebral infarction, developed hypophosphatemia associated with diabetic ketoacidosis and was treated with intravenous phosphate resulting in a rise in serum phosphorus from 0.9 to 6.1 mg/dL. Renal biopsies performed on both recipients for suboptimal kidney function revealed acute tubular injury and diffuse calcium phosphate microcrystal deposits in the tubules, which were persistent in subsequent biopsies. A retrospective review of preimplantation biopsies performed on both kidneys revealed similar findings. Even though initial renal histology in both recipients was negative for BK virus, they eventually developed BK viremia with nephropathy but both had a substantive virologic response with therapy. The first patient returned to dialysis at 6 months, while the other has an estimated glomerular filtration rate of 12 mL/min, 17 months following his transplant. We conclude that unrecognized acute phosphate nephropathy in a deceased donor contributed substantially to poor graft outcome in the two recipients.