Saturday, November 2, 2019
Indications for islet transplantation
1. Islet transplantation alone (ITA) is indicated for life-threatening hypoglycaemic unawareness.
2. Islet after kidney transplantation (IAK), where patients are already taking immunosuppression and have life-threatening complications of their diabetes.
3. Autologous islet transplantation in patients with chronic pancreatitis undergoing pancreatectomy. Their pancreas is processed, the islets extracted and then infused into their liver.
Simultaneous pancreas and kidney (SPK, 80%)
The pancreas is transplanted at the same time as a kidney from the same deceased donor. The recipient is in kidney failure, and either on or within a few months of starting dialysis. This combination is a bigger surgical operation, but has the benefit that the kidney can be used as a surrogate to monitor rejection of both grafts.
Transplantation For Diabetes Mellitus
Diabetes mellitus is characterised by high blood sugars due to insufficient insulin or insensitivity to the actions of insulin.
Chronic Renal Allograft Dysfunction
Chronic, progressive loss of allograft function beginning months or years after transplant may have a number of causes, both immunological and non-immunological. Previously, the terms chronic rejection or chronic allograft nephropathy were used to describe this gradual attrition of graft function. However, the most recent Banff classification advises distinguishing chronic antibody-mediated rejection (as evidenced by vascular changes and persistent C4d staining on biopsy in the presence of donor-specific antibodies [DSA]) from interstitial fibrosis and tubular atrophy (which can be caused by a number of factors, including chronic hypertension and CNI).
Thursday, August 22, 2019
Immunologically mediated allograft damage or rejection may be hyperacute, acute or chronic. Acute rejection is classified as acute cellular/T cell-mediated rejection or acute antibody-mediated/ humoral rejection, according to which arm of the immune system is principally involved in mediating allograft damage.
Saturday, July 6, 2019
Delayed Graft Function
One of the most common complications occurring in the early post-transplant period is delayed graft function (DGF). Clinically, the patient is oliguric, fails to demonstrate an improvement in renal function, and will often require haemodialysis. It is important to note that allograft oliguria may not be obvious in renal transplant recipients who have significant residual native urine output. In such cases, the patient may return from theatre passing good volumes of urine (resulting from the intravenous fluids given intra-operatively), all of which originate from their own kidneys. It is therefore important to ascertain from the patient their usual urine output and interpret post-transplant urine output in light of this information.
Kidney Transplantation: The Operation
The donor kidney
Renal anatomy and an malies
Most kidneys have a single artery and vein, although the incidence of multiple vessels is significant (10–20%). Multiple arteries usually arise close to each other, although a lower pole artery sometimes arises from the iliac artery instead of the aorta; others may take origin anywhere along the abdominal aorta, although most arise at or just below the origin of the superior mesenteric artery. Multiple veins may also occur, more commonly on the right than the left; when they do occur on the left the caudal vein sometimes passes behind the aorta; the left renal vein invariably passes in front.
Double ureters may also occur, although in the vast majority of cases only a single ureter is present.
Assessment For Kidney Transplantion
Although renal transplantation improves both quality of life and survival, it involves a significant investment of health resources and the use of an organ with a limited supply. It is therefore of utmost importance that the potential transplant recipient is carefully assessed, both to avoid unnecessary exposure to the risks of a general anaesthetic and to ensure appropriate use of a precious resource. To this end, every potential transplant recipient is assessed by taking a careful history, performing a thorough examination and undertaking a number of investigations.
Friday, June 14, 2019
Dialysis and its complications
Once a patient’s glomerular filtration rate (GFR) falls below 15 ml/ min/1.73m2 they require renal replacement therapy (RRT), either haemodialysis (HD), peritoneal dialysis (PD) or transplantation. Both haemo-and peritoneal dialysis are associated with specific complications, in addition to the general complications associated with ESRF.
Complications of ESRF
Normally functioning kidneys accomplish a number of important tasks.
1. Control of water balance.
2. Control of electrolyte balance.
3. Control of blood pressure (through both control of water and electrolyte balance and production of renin).
4. Control of acid-base balance.
5. Excretion of water-soluble waste.
6. The production of active vitamin D (though the action of 1α hydroxylase) and hence control of calcium-phosphate metabolism.
7. The production of erythropoietin (EPO), and hence control of haemoglobin concentration.
In patients with ESRF, one or more of the above functions cannot be performed, resulting in a number of complications.
Friday, May 31, 2019
End-Stage Renal Failure
End-stage renal failure (ESRF), as evidenced by a decline in glomerular filtration rate (GFR) such that function is inadequate for health, is relatively common and the prevalence increases with age. It can be classified in two ways, either, according to its temporal progression, or according to its cause.
Risk of CMV infection post transplant Cytomegalovirus (CMV) is a γ-herpes virus and is one of the most common infections encountered post-transplant. The likelihood of infection post-transplant is dependent on whether the recipient has had previous CMV infection and therefore has immunological memory of the virus. Immune memory is detected by looking for the presence of CMV-specific antibody (IgG).
The use of immunosuppressive therapy has led to a significant reduction in rejection, and a consequent improvement in graft and patient survival. Thus, many transplant recipients will be exposed to immunosuppressants for years or even decades. One of the major complications of prolonged immunosuppression is an increased risk of malignancy, particularly those driven by oncoviruses such as human papilloma virus (HPV) and Epstein-Barr virus (EBV). In addition, immunosuppressive drugs inhibit immune tumour surveillance, potentiate the effects of other carcinogens such as ultraviolet (UV) light, and some agents directly promote tumour formation or progression (for example ciclosporin stimulates vascular endothelial growth factor [VEGF]-A-associated tumour vascularisation and increases TGF-β production).
Friday, May 17, 2019
Following transplantation, patients are given immunosuppressive agents to prevent rejection. Unfortunately, this inevitably increases susceptibility to infection. Post-transplant immunosuppression has significant effects on T lymphocytes, hence many of the opportunistic infections seen are similar to those observed in patients with HIV, particularly cytomegalovirus (CMV) and Pneumocystis jiroveci (previously called P. carinii). In the early post-transplant period (months 1–3), immunosuppression is relatively intense, and therefore the patient is at particular risk of more unusual, opportunistic infection. In addition, some immunosuppressive agents are more powerful than others, e.g. lymphocyte-depleting agents such as ATG. Use of ATG at induction carries a higher risk of subsequent infection than the use of non-depleting biological agents such as anti-CD25 monoclonal antibodies. When considering infections occurring post-transplant, they can be divided according to causative agents.
Side Effects Of Immunosuppressive Agents
Immunosuppressants are necessary to prevent allograft rejection, but these agents have a number of unwanted side effects. These include generic side effects associated with all immunosuppressive agents, such an increased susceptibility to infection and malignancy, and drug-specific side effects.
T Cell-Targeted Immunosuppression
The most common form of rejection encountered is T cell-mediated (TMR) (also known as acute cellular rejection (ACR)), occurring in 15–20% of transplants. ACR is characterised histologically by lymphocyte infiltration into the graft (predominantly cytotoxic [CD8] T cells). ACR is orchestrated by CD4 T cells, which are activated by antigen-presenting cells (APCs), such as dendritic cells and B cells, presenting donor antigen to CD4 T cells via MHC class II molecules. For full activation of T cells, APCs also provide a co-stimulatory signal via surface molecules such as CD80/86. Such activated T cells produce large quantities of cytokines, particularly interleukin (IL)-2, which further drive the activation and proliferation of both CD4 and CD8 T cells. Thus, immunosuppressive agents predominantly target T cell activation via four broad mechanisms.
Polyclonal antibodies, such as anti-thymocyte globulin (ATG) and anti-lymphocyte globulin (ALG), are prepared by inoculating rabbits or horses with human lymphocytes or thymocytes and collecting their serum following immunisation. The IgG fraction is purified, but contains antibodies not only to lymphocytes, but also to platelets and red cells. ATG and ALG are fully xenogeneic and are therefore recognised by the recipient’s immune system as foreign, resulting in the development of neutralising antibodies. This prevents recurrent use. Despite this limitation, the lack of specificity and the development of a first-dose reaction, the so-called ‘cytokine release syndrome’ that follows cell lysis in up to 80% of patients, ATG is still used to treat steroid-resistant rejection.
Following organ transplantation, the recipient’s immune system identifies the graft as non-self by virtue of differences in donor cell surface markers, such as MHC molecules. An immune response against the graft follows, which will result in the loss of the transplanted organ, unless immunosuppressive agents are used to dampen the immune response.