Differences in Proinflammatory Cytokines and Monocyte Subtypes in Older as Compared With Younger Kidney Transplant Recipients.

Background:The number of elderly patients with end-stage kidney disease requiring kidney transplantation continues to grow. Evaluation of healthy older adults has revealed proinflammatory changes in the immune system, which are posited to contribute to age-associated illnesses via "inflamm-aging." Immunologic dysfunction is also associated with impaired control of infections. Whether these immunologic changes are found in older kidney transplant recipients is not currently known, but may have important implications for risk for adverse clinical outcomes. Methods:Three months after transplant, innate immune phenotype was evaluated by flow cytometry from 60 kidney transplant recipients (22 older [≥60 years] and 38 younger [<60 years old]). Multiplex cytokine testing was used to evaluate plasma cytokine levels. Younger patients were matched to older patients based on transplant type and induction immune suppression. Results:Older kidney transplant recipients demonstrated decreased frequency of intermediate monocytes (CD14++CD16+) compared with younger patients (1.2% vs 3.3%, P = 0.007), and a trend toward increased frequency of proinflammatory classical monocytes (CD14++CD16-) (94.5% vs 92.1%) (P = 0.065). Increased levels of interferon-gamma (IFN-γ) were seen in older patients. Conclusions:In this pilot study of kidney transplant recipients, we identified differences in the innate immune system in older as compared with younger patients, including increased levels of IFN-γ. This suggests that age-associated nonspecific inflammation persists despite immune suppression. The ability to apply noninvasive testing to transplant recipients will provide tools for patient risk stratification and individualization of immune suppression regimens to improve outcomes after transplantation

Cell-Free DNA and Active Rejection in Kidney Allografts

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P1% indicate a probability of active rejection

Transplanting kidneys from donors with prior hepatitis B infection: one response to the organ shortage

While the number of cadaveric organ donors remains relatively stable, the number of patients awaiting transplantation continues to increase, creating a shortage of donor organs. To address this imbalance, there is interest in transplanting organs formerly considered marginal or undesirable. Thus, more organs are currently transplanted from living donors, older donors, hemodynamically unstable donors, non-heart-beating donors and donors with markers of prior hepatitis B virus (HBV) infection. A large number (up to 93.8%) of liver transplant seronegative recipients from anti-HBc antibody positive donors have acquired HBsAg after liver transplantation in the absence of immunoprophylaxis. Based on experience in liver transplantation programs, transmission of HBV from donors without HBsAg but with antibody to HBV core antigen (anti-HBc), although conventionally defined as evidence of resolved infection, can have adverse consequences on both graft and recipient. On the contrary, HBV appears to be in-frequently transmitted from HBsAg negative/anti-HBcAb positive kidney donors: the incidence of de novo HBsAg seropositivity after renal transplantation ranges between 0 and 5.2%. A significantly higher incidence of anti-HBc antibody seroconversion (without developing HBsAg) after renal transplantation with anti-HBc antibody positive donors was seen. However, anti-HBc antibody positive renal allografts should be considered, especially for recipients who have been successfully immunized with HBV vaccine. Prospective long-term studies are in progress to assess the risk of de novo HBV infection (HBsAg seroconversion) in renal transplant recipients who have not been successfully immunized with vaccine against HBV

Treatment of Hepatitis C in Potential Kidney and Heart Transplant Patients

Hepatitis C virus (HCV) is common in certain solid organ transplant recipients, most notably in those undergoing liver or kidney transplantation. Infection typically antedates transplantation but may have been acquired at the time of transplantation via infected blood products or organs. A more rapid and aggressive course of HCV-related infection and liver disease is the major concern in organ transplant recipients compared with immunocompetent patients. HCV-related liver disease is an important cause of morbidity and mortality in patients with end-stage renal disease treated by dialysis or transplantation. The outcome of HCV infection in renal and liver transplant recipients has been extensively investigated, whereas literature on HCV-related liver disease among patients with orthotopic heart transplantation is scanty. This article reviews the literature concerning the treatment of HCV-related liver disease in renal and orthotopic heart transplantation

Management of Renal Dysfunction in Patients Receiving a Liver Transplant

Renal dysfunction is a frequent complication in patients with endstage liver disease awaiting orthotopic liver transplantation. Although the stereotypical form of renal dysfunction is the hepatorenal syndrome, common causes of acute kidney injury include prerenal azotemia and acute tubular necrosis in this population. Management involves hemodynamic support, renal replacement therapy, and mitigation of risk factors. Renal dysfunction in a cirrhotic patient usually implies a poor prognosis in the absence of liver transplantation. An important issue is the frequent need for kidney, in addition to liver, transplantation if renal insufficiency has been persistent in a decompensated cirrhotic