Kidney transplantation outcomes in patients with IgA nephropathy and other glomerular and non-glomerular primary diseases in the new era of immunosuppression.

OBJECTIVES: Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. METHODS: Ninety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN). RESULTS: At end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (p<0.0001) in the FSGS group, 42.1% (p = 0.17) in the IMN group, and 0% in the LN and PIGN groups (p = 0.01). IgAN recipients, who were maintained with a regimen containing tacrolimus, experienced recurrence less frequently, compared to those maintained with cyclosporine (p = 0.01). Graft loss attributed to recurrence was significantly higher in patients with FSGS versus all others. CONCLUSION: Recipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

Glomerular Diseases Associated with Malignancies: Histopathological Pattern and Association with Circulating Autoantibodies.

AIM: Glomerular diseases (GD) associated with malignancies (AM, GDAM) have unique features, which are important to recognize, in the light of the progress made in cancer therapy. We aimed to describe the clinical and histopathological characteristics of patients with GDAM in relation to the presence of circulating autoantibodies, pointing to potential immune pathogenic pathways connecting cancer to GD. MATERIALS AND METHODS: The included patients were studied retrospectively on the basis of a kidney biopsy proving GD and a related biopsy to establish the diagnosis of AM. We recorded patients' demographics, serological and laboratory parameters, histopathological findings, and the type of malignancy, GD, and therapy. RESULTS: In total, 41 patients with GDAM, with a mean age of 63.1 (±10.7) years, were studied. In 28 (68.3%) cases, GD was associated with a solid tumor, and in 13 (31.7%) patients with a lymphoid malignancy. The most frequent histopathological pattern was membranous nephropathy (43.9%). Overall, at the time of GD diagnosis, 17% of the patients were positive for antinuclear antibodies (ANA), and 12.2% for antineutrophil cytoplasmic autoantibodies (ANCA), all against myeloperoxidase (MPO). In addition, 93.3% of the patients who had membranous nephropathy were negative for transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) antibody. Sixteen patients (39.0%) presented with acute nephritic syndrome, of whom five (31.25%) developed rapidly progressive glomerulonephritis. In a mean follow-up time of 36.1 (±28.3) months, nine (21.95%) patients ended up with end-stage kidney disease, and eight (19.5%) died. CONCLUSION: We found that 3.2% of patients who underwent a native kidney biopsy in our institution during the past decade, for any reason, were identified as having some type of GD associated with a malignancy. Serology indicated a significant presence of ANA or MPO-ANCA antibodies in patients with nephritic syndrome and the absence of PLA2R antibodies in patients with membranous nephropathy.

The clinical course of IgA nephropathy after kidney transplantation and its management.

Immunoglobulin (Ig) A nephropathy is one of the most common primary glomerulonephritides worldwide causing end stage renal disease in up to 20-40% of affected patients, nearly two decades post diagnosis. Kidney transplantation is the treatment of choice for patients with renal failure, secondary to glomerular diseases. However, IgA nephropathy has a strong tendency to recur in the graft, and although initially thought to be a benign condition, several reports of graft loss, due to recurrent IgA nephropathy, there have been over the last three decades. Overall graft survival has been significantly improved in kidney transplantation, as a result of reduced incidence of acute rejection, as more potent and more specific immunosuppressive agents are now available in clinical practice. Thus, the rates of IgA nephropathy and other glomerulonephritides recurrence are expected to increase, since graft survival has been improved. However, the reported incidence of IgA nephropathy recurrence in the graft varies substantially across centers, as a consequence of different levels of interest, diverse biopsy policies and differing durations of follow up, of the published studies. Notably, recurrence rates of patients receiving graft biopsies by clinical indication only, ranges from 13% to 50% with graft loss being between 1.3% and 16%. The aim of this review is to underline important pathogenetic insights of IgA nephropathy, describe the clinical course of the disease after kidney transplantation, with emphasis on the incidence of recurrence and the associated risk factors, and finally provide all available options for its management in transplant recipients.

Clostridium difficile infection among kidney transplant recipients: frequency, clinical presentation, and outcome.

The objective of this study was to evaluate the frequency of Clostridium Difficile Infection (CDI) among kidney transplant recipients and describe the clinical picture in correlation with the presence of certain risk factors. We included kidney transplant recipients with a functioning graft, who were admitted during the period 1/2012-12/2013, and patients with ESRD who were admitted to undergo Kidney Transplantation (KTx) from a deceased or a living donor in the same period. Patients were screened following clinical indication of gastrointestinal infection. CDI diagnosis was based on a positive stool sample for CD toxins and stool culture. Within the period 2012-2013, we recorded 24 cases of CDI in 19 patients, accounting for a frequency of 5.4% of CDI in our population. In addition to diarrhea, 63.15% of the patients presented with fever, 31.25% with anorexia, while abdominal pain was a rare symptom (0.53%). None of the patients had ileus, bowel obstruction or megacolon. Fourteen patients (73.7%) had a history of recent exposure (15 days) to antimicrobial agents prior to the evolution of CDI symptoms. A relapse of the CDI infection was identified in five cases. CDI infection is a significant factor of morbidity in patients with KTx and should be considered in the clinical setting of diarrhea, even in cases with no exposure to antibiotic agents.

Incidence and clinical significance of de novo donor specific antibodies after kidney transplantation.

Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients.