Significance of subclinical rejection in early renal allograft biopsies for chronic allograft dysfunction

To determine the significance of early subclinical rejection of renal allografts, we reviewed 127 biopsy specimens obtained soon after transplantation. Histological finding was categorized according to a modification of the Banff scheme as: acute rejection (AR), borderline changes (BL); non-specific inflammatory changes, (NI) and no rejection (NR). Subclinical rejection was defined as AR, BL or NI. Patients with BL or NI were divided into two groups; one was treated with high-dose methylprednisolone (MP), the other remained untreated. Freedom from chronic allograft dysfunction (defined as non-doubling of serum creatinine 5 yr after transplantation) was significantly more frequent in the NR group (89%) than in the BL (70%) and AR (64%) groups. At 1 yr after transplantation, mean serum creatinine had increased significantly only in the untreated group (p < 0.05), and re-biopsy showed that interstitial fibrosis had developed to a significantly greater extent in the untreated group than in the treated group (p < 0.01). Subclinical rejection in the early protocol biopsies correlated closely with subsequent allograft dysfunction. High-dose MP treatment for early subclinical rejection may be effective in suppressing the development of interstitial fibrosis at 1 yr after transplantation.     

The significance of subclinical rejection

Abstract:  Subclinical rejection (SCR) is quite common early following renal transplantation and decreases progressively with time. The immunological profile of the recipient, the immunosuppressive regimen used, and the occurrence of prior episodes of clinical acute rejection (AR) are all risk factors for SCR. SCR, in turn, is a risk factor for chronic interstitial and tubular fibrosis and has been associated with worse glomerular filtration rate (GFR) and graft survival. Early SCR should be initially treated with pulse steroids. SCR is a form of biopsy-proven AR and, particularly if treated, must be fairly reported and displayed as a solid endpoint in clinical studies.     

Refractory acute kidney transplant rejection with CD20 graft infiltrates and successful therapy with rituximab

Acute rejection is an expected event after transplantation and has been associated with poor long-term kidney transplant outcome. The presence of B cells in the kidney graft with acute rejection is thought to be an omnious sign, as it has been associated with poor graft outcome. There is no definitive treatment for acute rejection with B cells in the graft. Rituximab, a humanized monoclonal antibody against CD20, has been used in the treatment of B cell lymphoma. We present the case of a 49-yr-old Caucasian male with early acute kidney allograft rejection that was refractory to high doses of steroids and rabbit anti-thymocyte globulin (thymoglobulin). Repeat renal biopsy revealed T cell and B cells in the kidney graft and responded to the combination of rituximab and muromonab (a mouse monoclonal antibody to CD3 receptor). Over 9 months post-transplant, the patient remains rejection free with a serum creatinine of 1.7 mg/dL.     

Acute colitis associated with dengue fever in a renal transplant recipient

Dengue fever is a significant health problem for international travelers to all endemic area. Dengue fever is characterized by a sudden onset of fever, headache, rash, myalgia, and joint pain. Infection with the dengue virus is detrimental to a immunosuppressed renal transplant patients. Herein we report a 29-year-old woman living-related renal transplant recipient returning from Southeast Asia with dengue fever presenting as acute colitis. The patient traveled to Southeast Asia for 1 week. She developed watery diarrhea in the second week after the onset of symptoms of dengue fever. Laboratory findings were leukopenia, thrombocytopenia, and elevated serum transaminase levels. Sigmoidoscopic features showed nonspecific acute colitis. She improved after 10 days of hospitalization with intensive supportive care and continuous tacrolimus monotherapy. Altered clinical symptoms are manifested in immunologically na?ve adults. Manifestation of unusual symptoms does not exclude dengue virus infection in renal transplant recipients.     

A rare case of vascular rejection in a renal transplant recipient with nephrotic range proteinuria

Abstract:  In the post-cyclosporine A era, it has been reported that acute rejection after kidney transplantation is commonly revealed as an asymptomatic increase in the serum creatinine level. Nephrotic range proteinuria is observed in patients with recurrent or de novo glomerulonephritis, or with chronic transplant nephropathy and glomerulopathy in the late phase. Acute rejection occurring with nephrotic range proteinuria without a rise of serum creatinine has been rarely reported. Here, we report a rare case of vascular rejection in a renal transplant recipient with nephrotic range proteinuria. A 34-yr-old male renal transplant recipient presented with acute vascular rejection and early-onset nephrotic syndrome. Severe nephrotic range proteinuria was detected with a minimally elevated level of serum creatinine. Biopsy showed severe glomerulitis and vasculitis, which was relieved by conversion of the immunosupressant regimen. Severe proteinuria was a sign of acute vascular rejection with severe glomerulitis and vasculitis. Careful observation to ensure maintenance of immunosuppression is necessary in such cases.     

Clinical remission and pathological progression after tonsillectomy in a renal transplant patient with recurrent IgA nephropathy

Abstract:  We discuss a renal transplant patient with recurrent IgA nephropathy (IgAN) before and after tonsillectomy. A 36-year-old man started on hemodialysis support in 1996 due to biopsy-proven IgAN, living related renal transplantation was then performed in 1997. Six years after transplantation, the patient presented with microhematuria and proteinuria. Graft biopsy for these urinary abnormalities showed recurrent IgAN. Tonsillectomy was subsequently performed in December 2003, proteinuria remitted 6 months after the tonsillectomy and microhematuria disappeared three years later. Protocol graft biopsy was subsequently performed twice, at 2 yr after the tonsillectomy (2005) and 4 yr after (2008). Comparing the findings of the pre-tonsillectomy biopsy and the two post-tonsillectomy biopsies, an increase in mesangial cells and matrix in 2005, and an expansion of the mesangial matrix and proliferation of mesangial interposition in 2008. In addition, global sclerosis of glomeruli increased over time, the area of tubulointerstitial damage has extended as well. While the tonsillectomy led to clinical remission of recurrent IgAN, the chronicity progressed on these protocol biopsies. This is the first report of the efficacy and the limitations of tonsillectomy in a case of recurrent IgAN in a transplant patient.     

Myoglobinuria masquerading as acute rejection in a renal allograft recipient with recurrent post transplant diabetic nephropathy

Rhabdomyolysis contributes to 7–10% of total AKI cases. Myoglobinuria as a cause of acute renal allograft dysfunction is extremely uncommon. Renal allograft recipient on cyclosporine or tacrolimus can develop myoglobinuria in presence of other precipitating factors. Present case describes an interesting report of myoglobinuria in a patient with post transplant diabetic nephropathy mimicking acute graft rejection. Clinically myoglobinuria presenting as renal allograft dysfunction is diagnosis of exclusion and renal biopsy is extremely important in making a correct diagnosis and planning optimal management in such cases.     

Late onset Pneumocystis pneumonia in patients receiving rituximab for humoral renal transplant rejection

Rituximab has been used increasingly in the treatment of antibody-mediated rejection (AbMR) in solid organ transplantation despite the absence of clinical trials demonstrating efficacy. A contributor to the growing use of rituximab is an apparent lack of morbidity; and there are no reports of specific opportunistic infections associated with its use in renal transplant recipients. Two cases of Pneumocystis pneumonia (PCP) occurring nearly 3 years after administration of rituximab for refractory AbMR are reported herein. These cases emphasize the need for ongoing vigilant observation in patients who have received rituximab, and highlight the importance of clinical trials to establish the role of rituximab in prevention and treatment of AbMR.     

An unusual presentation of sirolimus associated cough in a renal transplant recipient

Sirolimus-associated pulmonary problems are rare but life threatening. Pulmonary problems due to sirolimus treatment are interstitial pneumonitis, bronchiolitis obliterans organizing pneumonia (BOOP), and alveolar hemorrhage. We present a case of sirolimus-related cough in the absence of any pulmonary radiological findings. A 55-year-old man with a history of 4 years of hemodialysis therapy because of end-stage renal disease of unknown etiology underwent cadaveric renal transplantation in June 2006. Three days following the initiation of sirolimus therapy he complained of dry cough and fever. There were no clinical or laboratory findings compatible with specific pulmonary disease. After switching sirolimus to tacrolimus, the cough improved within 1-2 days and resolved in 5 days. Sirolimus should be considered in the differential diagnosis of pulmonary problems in the early posttransplantation period even in the absence of radiological findings.     

Pyocystis in a renal transplant recipient with a defunctionalized bladder

Fever occurred in a man 6 weeks after renal transplantation. At the time of transplantation, the donor ureter had been anastomosed to a ureteroileal conduit created 6 years previously because of traumatic neurogenic bladder. Initial evaluation failed to reveal the cause of the fever, but ultimately, drainage of the defunctionalized bladder yielded a large amount of pus infected with Klebsiella pneumoniae. Our patient's course suggests that, when fever develops after renal transplantation in patients with previous urinary diversion, pyocystis should be included in the differential diagnosis.