Implications of immunohistochemical detection of C4d along peritubular capillaries in late acute renal allograft rejection.

BACKGROUND: Immunohistochemical detection of the C4d complement product along peritubular capillaries (PC) may indicate humoral rejection of renal allografts. We examined the frequency of PC C4d expression in renal-allograft biopsies with acute rejection (AR) arising more than 6 months after transplantation and the impact of this finding. METHODS: C4d was detected by immunoperoxidase in 2-micron paraffin sections of consecutive biopsies obtained over a 3-year period. The extent was classified as diffuse (> or =50% PC C4d+), focal (<50% C4d+), and negative (C4d-). Clinical data were obtained by retrospective chart review. Fifty-five AR episodes with Banff 97 types 1A (n = 13), 1B (n = 26), 2A (n = 11), 2B (n = 3), and 3 (n = 2) met inclusion criteria. RESULTS: PC C4d expression was diffuse in 23 (42%), focal in 9 (16%), and negative in 23 (42%) biopsies. AR episodes with focal and diffuse C4d expression had higher proportionate elevation of serum creatinine at biopsy and 4 weeks after diagnosis (P< or =0.05). Biopsies with diffuse PC C4d had interstitial hemorrhage (56.5%) and plasmacytic infiltrates (52%) more frequently than C4d- biopsies (22% and 16%), P = 0.02, but had no other distinctive histologic features. Graft loss was greater in diffuse (65%) compared with focal C4d+ (33%) and C4d- (33%) groups 1 year after diagnosis, P = 0.03. Other clinical and pathologic parameters did not differ significantly, including treatment received for AR. CONCLUSION: Evidence of acute cellular with occult humoral rejection is identified in more than 40% of late AR episodes. Late acute humoral rejection may be associated with interstitial hemorrhage and plasma cells and contributes significantly to graft loss.

Treatment of de novo and recurrent membranous nephropathy in renal transplant patients.

Membranous nephropathy (MN) is one of the common glomerular diseases diagnosed in transplanted kidneys. The exact impact of posttransplantation MN on the risk for graft loss and long-term graft outcome is not defined clearly. In recent reports, it has emerged as the third most frequent glomerulonephritis (de novo or recurrent) associated with renal allograft loss. Most cases of posttransplantation MN are thought to be idiopathic but cases associated with established secondary causes also have been reported. Patients can present with varying degrees of proteinuria and graft dysfunction. Risk factors that predict a poor outcome are not well established and unlike MN in the native kidneys, spontaneous remission is rare. Patients should be evaluated carefully for complications associated with nephrotic syndrome or graft dysfunction and managed accordingly. The beneficial effects of steroids, cyclosporine, mycophenolate mofetil, cyclophosphamide, chlorambucil, or other agents have not been validated. The role of specific treatments in cases of secondary MN is uncertain. Retransplantation is a reasonable option for patients who develop graft failure secondary to MN.

Hyperphosphatemia in dialysis patients: is there a role for focused counseling?

BACKGROUND: Elevated serum phosphorus (P) and calcium-P product (CaXP) are associated with cardiac mortality in dialysis patients. A CaXP <55 is considered acceptable by most authorities. Because nutrition practices can modulate CaXP, we designed a survey to study the impact of the patients' levels of education and disease awareness on their CaXP. METHODS: A survey questionnaire with 5 didactic questions pertaining to hyperphosphatemia and P-binders and 5 questions related to patient attitudes and beliefs was administered to all patients in a hemodialysis unit. The association of CaXP >55 with the patients' level of education, their score on the survey (didactic part, score 0 to 5), parathyroid hormone (PTH) levels, hyperkalemia, hypertension, and vascular disease were studied. RESULTS: Of the 117 patients (61 men, age 56.5 +/- 18 years) who participated in the survey, 49 (42%) had CaXP >55 and 100 (85%) were on P binders. Thirty-seven (31.6%) had at least some college education. Eighty-seven patients (74%) failed to identify foods rich in P; 61% were unaware of complications related to high CaXP. Patients with CaXP >55 were less likely to have college education (20% versus 39%, P =.04), and had lower survey scores (2.4 +/- 1.3 versus 2.6 +/- 1.4, P = NS). Patients with college education scored higher (2.9 +/- 1.1 versus 2.3 +/- 1.4, P =.014). Furthermore, CaXP >55 was significantly associated with hyperkalemia (P =.02), high PTH levels (P <.001), and hypertension (P =.02), but not with >Kt/V, URR, type of hemodialysis access, or vascular diseases. CONCLUSION: The majority of patients in the survey were ignorant of basic facts pertaining to high P and CaXP. The association of CaXP >55 with hyperkalemia, and not with Kt/V, suggests dietary noncompliance rather than inadequate dialysis. Patients with less education were more likely to have CaXP >55. Because this related mostly to misperception of simple facts that affect dietary habits, there is need for focused counseling of these patients at a level appropriate for their literacy skills.

Successful retransplantation after renal allograft loss to polyoma virus interstitial nephritis.

BACKGROUND: Although polyoma virus infection is being increasingly recognized as a cause of renal allograft dysfunction and failure, the risk of polyoma recurrence in a subsequent transplant is unknown. We present the first reported case of successful retransplantation after polyoma virus-induced renal allograft loss. CASE REPORT: A 40-year-old Caucasian woman received a cadaveric kidney transplant. Baseline immunosuppression included corticosteroids, mycophenolate mofetil, and tacrolimus. Her post-transplant clinical course was complicated by an early acute rejection episode on posttransplant day (PTD) 6, that warranted treatment with OKT3. A biopsy performed on PTD 154 to evaluate a rise in creatinine revealed polyoma virus interstitial nephritis. Despite reduction in immunosuppression, the renal function progressively worsened and dialysis was initiated by PTD 160, followed by transplant nephrectomy on PTD 184. Four months later, she received a living related kidney from her sister. Immunosuppression was initiated with prednisone, azathioprine, and tacrolimus. She had immediate graft function with a decrease in serum creatinine from 12.8 to 1.1 mg/dl. Three and one-half years after her second renal transplant, her allograft functions well, with a serum creatinine of 1 mg/dl. Both quantitative and qualitative assays of blood and urine (by PCR) remain negative for BK virus, indicating the absence of virus reactivation. CONCLUSION: Judicious retransplantation should be considered as a therapeutic option in the management of polyoma virus induced graft failure. Previous graft loss secondary to polyoma virus infection is not a contraindication to retransplantation.