End Stage Renal Disease: Management Issues

The patents with end stage renal disease (ESRD) need regular hemodialysis or renal replacement (kidney transplantation) for survival. Both the hemodialysis and kidney transplantation are very costly procedures for the patients and their families. The patients with chronic kidney disease (CKD) are at high risk of developing end stage renal disease (ESRD). Chronic kidney disease (CKD) is diagnosed on the basis of persistently high level of serum creatinine (more than 1.8 mg/dl). As a rough estimate one person in every 150 people may be suffering from CKD and around 3% of CKD cases are sure to develop ESRD. In a country with 500 million population there could be more than 100,000 patients with ESRD and around 3.5 million patients with CKD. Half of the projected figures could be annual incidence.

It has been worked out that the cost of annual dialysis is much more than the renal replacement therapy (RRT). Though the renal transplantation (kidney transplantation) is the more effective and sustainable therapy but the economic factors, availability of kidney and facilities retard its scope. The annual cost of dialysis may range from US$5000 to 10,000 depending on condition of the patient; whereas the one-time cost of renal transplantation at government funded hospitals in most of the developing countries ranges from US$1500 to US$2000 and annual cost of immunosuppressive therapy would be around US$3000 to 4000. As compared to patients on dialysis, the quality of life for the patients of renal transplantation is extremely better. A renal transplantation at an optimum time minimizes the graft maintenance costs and maximizes the graft survival. The patient can return to productive life within a year after renal transplantation. My friend AB, who got renal transplantation around 10 year ago, is living a normal life.

Renal Transplantation and Immune Profiling

Organ transplantation is analogous to blood transfusion and we need to detect and match the tissue antigens of the donor and the recipient before transplantation of an organ, say kidney. Tissue antigens are known as human leucocyte antigens (HLA). There are four loci called A, B, C and D on the 6th chromosome, which govern these tissue antigens or HLA. We inherit one gene (each gene has sub-genes) each on each locus from our mother and father. There is antigenic polymorphism at each locus (A, B, C, and D). Unless the kidney donor and the recipient (patient) are identical twins, a 100% match of these HLA is not possible. There is 50% match of HLA amongst parents and children, and the siblings. Unrelated donor and recipient may also have 50% matching of tissue antigens or HLA. The participation of immune mechanisms in allogenic kidney transplant begins with the identification and appropriate reaction to the donor organ, by the recipient, depending on the degree of HLA mismatch. Immunosuppressive therapeutic protocols are prescribed for the adoption and survival of grafted/transplanted kidney. There is very complex immune pathway in our body involving antigen presenting cells and T & B cells (Lymphocytes), which get activated and lead to injury of the target cells. The intragraft cell trafficking and their effector mechanisms may have serious implications. Post transplant immune profiling is a way of monitoring the allograft function and to elucidate pathogenic mechanisms and molecular pathways causing tissue injury and disease.

Transplant tolerance could only be achieved through sincere compliance of immunosuppressive therapy. The immune system of the recipient following renal transplantation, though challenged by the exposure to donor antigens to initiate an early sub-clinical or acute rejection process, attempts to regulate the inflammatory processes or maintain homoeostasis in the body. The acute rejection may be cell or antibody mediated. The transplant tolerance is defined as maintenance of stable allograft function without clinical evidence of immunosuppression. There are many therapeutic approaches to achieve the transplant tolerance, however, the best one is donor specific transfusion or hematopoietic cell infusion. Almost all the transplant recipients have to depend on a variety of immunosuppressive protocols to ward of any chance of allograft rejection.

End Stage Renal Disease and Renal Transplantation

Chronic glomerulonephritis, diabetic nephropathy, chronic tubulointerstitial disease, benign nephrosclerosis and polycystic kidney disease are the major causes of end stage renal disease (ESRD) and renal failure. Patients with ESRD exhibit a variety of abnormalities in their autonomic functions. Precise mechanisms of evaluating autonomic functions have revealed abnormalities in efferent parasympathetic pathway and baroreceptor sensitivity in patients with end stage renal disease. An increase in expiration-inspiration, lying standing and valsalva ratios, and baroreceptor sensitivity slope have been well documented in ESRD. Uremic patients with ESRD respond poorly to antihypertensive drugs as compared to otherwise healthy controls. Renal involvement in multiple myeloma is an other cause of ESRD and renal failure. Dialysis is an adoptive procedure in patients having end stage renal disease and ultimate surgical measure is renal (kidney) transplantation. Adequate dialysis in patients with ESRD reverses the elevated levels of urea, creatinine and electrolytes in blood.

Though renal transplantation is must in patients with ESRD, but it needs a lot of medication and post transplantation care for the successful adoption and survival of renal allograft. Systemic fungal infections (cryptococcosis, mucuromycosis, candidiasis, aspergillosis and mixed infections) have been documented after renal transplantation. Though these infections are treatable but may complicate the post operative care as additional medication will be required in addition to immunosuppressive therapy. High incidence of tuberculosis has also been observed in recipients of renal transplant along with viral infections like BK virus and cytomegalovirus (CMV). Adverse impact of pre-transplant polyoma virus (BK virus) infection on the graft survival has also been documented. Molecular technology has been developed for the early detection and identification of these viruses from the time of renal transplantation onwards by using protocol biopsies from the grafted kidney.