End-stage kidney disease (ESKD), the most serious and dramatic manifestation of kidney disease, is today a worldwide public health issue, especially in developing countries. In developed countries, advances in the main treatment modalities – dialysis and transplant – have significantly improved life expectancies. Indeed, innovative transplant surgical techniques, improved immunological risk assessment of donors and recipients, and better and more sophisticated immunosuppressive drugs have made renal transplantation a more effective treatment for patients with ESKD than long-term dialysis.
For underwriters, correctly assessing the potential mortality and morbidity risk of applicants who are past renal transplant recipients involves understanding a broad range of issues related to kidney disease, current transplantation science, long term graft success, post-transplant survival predictors, and the common causes of death in kidney transplant recipients.
Since the middle of the last decade, incidence rates for ESKD have stabilized for the world’s more affluent countries, but have continued to increase for developing countries. Higher-income countries’ renal health priorities, which are aimed at improving the detection of chronic kidney disease (CKD) in the hopes of delivering treatments to slow its progression, likely play a role in limiting the progression to Stage 5 CKD (ESKD).2 In developing countries, however, diabetes, hypertension, and communicable diseases that can lead to acute kidney injury all play important roles in the rising rates.2
Part of the reason is continued treatment inequities, which need to be addressed. In addition, especially in tropical nations, environmental factors such as the higher rates of bacterial, viral, and parasitic infections found in these countries contribute to a glomerular disease prevalence 2.5 times higher than that of developed countries.
CKD and ESKD – Basics
Chronic kidney disease (CKD) is diagnosed using three prognosticators: renal function (as indicated by estimated glomerular filtration rate [eGFR]), imaging results (whether ultrasound, CT, or MRI) showing kidney damage, and the proteinuria/creatinine (or albumin/creatinine) ratio.
The National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative (KDOQI), which provides evidence-based guidelines for all stages of CKD, currently recommends using serum creatinine concentration, expressed by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation, to calculate eGFR. Individuals with an eGFR of <60 ml/min/1.73m2 for three months, according to this guideline, are classified as having CKD, irrespective of the presence or absence of kidney damage. ESKD, which is Stage 5 CKD, is defined as an eGFR of <15 ml/min/1.73m2. Those at this eGFR level are candidates for permanent renal replacement therapy.
ESKD is considered to be caused primarily by diabetes, hypertension, glomerulonephritis (GN), and cystic diseases. Communicable diseases can also be causes. In the U.S., the most common ESKD etiologies are diabetes, hypertension, and GN. ESKD patients with GN as the primary cause are considered to have better prognoses than those whose ESKD is from other causes. However, these are the “primary” diagnoses for ESKD, assigned by the treating physician at the start of treatment. Quite commonly, the original etiology of the disease may be difficult to discern as renal patients are, unfortunately, frequently asymptomatic until they reach more advanced CKD stages.4
- focal segmental glomerulosclerosis (FSGS)
- IgA nephropathy (IgAN)
- membranous nephropathy
- membranoproliferative glomerulonephritis (MPGN)
- lupus nephritis (LN)
Large differences in patient mortality, as measured by the adjusted mortality hazard ratio (aHR), were found among the six groups. After adjustment for demographics and comorbidity, patients with IgAN (also known as Berger’s disease) had the fewest comorbidities and the lowest mortality. The next lowest were patients with membranous nephropathy (aHR 1.23), FSGS (aHR 1.37) and MPGN (aHR 1.38). The highest aHRs were in patients with LN (aHR 1.75) and diabetes (aHR 1.73), followed by vasculitis (aHR 1.51). Patients with IgAN were also found to have better survival rates than patients with autosomal dominant polycystic kidney disease (ADPKD), who are often considered to have among the best prognoses among patients with ESKD
Although this research partly illustrates the tendency for GN to become inactive and undifferentiated as kidney failure progresses to end stage (as may have occurred in our case study), it also raises questions, as there is no assurance that the diagnosis was based on biopsy. Also, an important prognostic factor is disease activity at onset of ESKD. This could be inferred by the presence or absence of immunosuppressive treatments given upon an ESKD diagnosis.
Transplantation has been an accepted ESKD treatment for the last 60 years. CKD patients are generally educated soon after their diagnosis about the natural progression of their disease, the different types of dialysis available, and the renal transplantation option.
The best evidence from observational data show that transplantation confers a mortality benefit in addition to improved quality of life compared with maintenance dialysis.
Indications for transplantation for patients with ESKD include:
- severe metabolic acidosis
- hyperkalemia (elevated potassium levels)
- clinical manifestations such as pericarditis, encephalopathy, and intractablevolume overload
- declining nutritional status
- a glomerular filtration rate of 5-9 ml/min/1.73m² in otherwise asymptomatic adults
Kidney donors can either be related or not to the recipient, and can be living or deceased as well. The degree of a transplant recipient’s immune response depends partly on the degree of genetic difference between an organ and its recipient. The human leukocyte antigen (HLA) system genes (or gene complex), which governs compatibility, are located on the short arm of the chromosome 6, and encode the major histocompatibility complex (MHC) proteins. These proteins are divided into class I
(HLA A, B and C) and class II (HLA DR, DQ and DP) antigens and are responsible for regulating the human immune system. The role of these proteins is to present peptides to T-cells, enabling them to recognize and eliminate “foreign” cells. The most common form of acute rejection of grafts involve a recipient’s T-cells (i.e. adaptive immune response) becoming activated against the donor’s MHC antigens.
Long-term renal graft survival has been shown to be closely related to the number of HLA mismatches at the time of transplantation.20 In our case study, the applicant had a low Panel Reactive Antibody (PRA) score and was fortunate to receive a kidney from a closely matched living donor.