From May 31 to June 3, 2014, the 51st Congress of the “European Renal Association” and the “European Dialysis and Transplant Association” (ERA-EDTA) was held in Amsterdam, the Netherlands. The consensus at the congress was that the number of people requiring renal replacement therapy will continue to increase in the coming years. Therefore, regional and international efforts are needed to promote the prevention of kidney disease, to improve the care of kidney patients and, if possible, to motivate more healthy people to donate kidneys.
Type 2 diabetes and obesity are two of the biggest health problems today. Worldwide, the number of patients with diabetes and obesity is increasing dramatically, and in parallel, the proportion of people with chronic kidney disease (CKD) is also increasing. Approximately 20-40% of individuals with diabetes and/or obesity develop renal dysfunction – as a result, many develop CKD and, at most, require dialysis, and their risk for cardiovascular disease is clearly increased. In ERA, the working group “Diabesity” deals with the pathogenesis of these diseases, because there are several links between them, e.g. insulin resistance. The working group focuses particularly on the prevention as well as the earliest possible diagnosis and treatment of renal dysfunction in “diabesity” patients.
Promote kidney donation – also from living kidney donors
The Congress also celebrated the 50th anniversary of the ERA-EDTA Registry. This organization collects data from dialysis and kidney transplant patients in 31 European countries (Switzerland is not included). Over the past 50 years, these therapeutic modalities have evolved from experimental treatments to routine therapies. Today, there are more than half a million people in Europe who are still alive thanks to dialysis or kidney transplantation. In the past, primarily younger and relatively healthy people received renal replacement therapy – today, patients are often older and suffer from a variety of comorbidities.
The incidence of renal replacement therapy varies widely between European countries: almost three times as many people are treated with renal replacement therapy in Portugal than in Finland and ten times as many as in Ukraine. The factors driving this disparity are being examined as part of research conducted by the ERA-EDTA Registry.
For patients with advanced renal failure, kidney transplantation is treatment of first choice because transplantation not only offers a survival benefit, but also a significantly better quality of life than dialysis. It therefore makes sense to make efforts that increase the number of living kidney donations. This is done, for example, in the Netherlands, where altruistic kidney donation is allowed between unrelated people; the slogan is “You have two kidneys – one for yourself and one to give to someone.” As a result of such efforts, Norway and the Netherlands have the highest rates of kidney transplantation in Europe. No such efforts have yet been made in Switzerland.
New guidelines for kidney transplantation
In recent years, the European Renal Best Practice Working Group of ERA-EDTA has substantially revised the European Guidelines for the Management of Kidney Donors and Recipients. The guidelines were published in 2013 and translated into more than 15 languages. The goal is to improve the quality of care for these patients with their complex health problems.
Study with bardoxolone discontinued due to side effects
The high mortality of patients with type 2 diabetes is strongly associated with the presence of nephropathy. Microinflammation and oxidative stress play important roles in pathogenesis. Bardoxolone, a prostaglandin-like substance, acts as an antioxidant anti-inflammatory. In phase II trials, bardoxolone was shown to be an effective nephroprotective agent, significantly improving glomerular filtration rate (GFR) over 52 weeks in patients with type 2 diabetes [1].
However, the phase III trial (BEACON), which had been started in June 2011, had to be stopped in October 2012 because the toxicity of the substance was too strong and mortality was slightly increased in the verum group [2]. It now appeared from the analysis of the study that the mechanisms that improve GFR (modulation of the endothelin pathway) also enhanced sodium and volume retention, leading to a wholly unexpected increase in heart failure cases [3]. Other common side effects were muscle cramps and hypomagnesemia.
Prevent progression of kidney disease with emapticap?
Further studies are currently being conducted with substances that are intended to prevent or slow down the progression of CKD. A phase II study with the active substance emapticap pegol was presented at the ERA-EDTA congress. The compound was injected subcutaneously twice weekly for 85 days in 75 patients with type 2 diabetes and albuminuria. Emapticap proved to be safe and almost free of side effects, and it was able to significantly reduce the average albumin-creatinine ratio by 32% [4]. The positive effects persisted during the twelve-week follow-up period. However, these results need to be assessed with caution and confirmed in a phase III trial – the example of bardoxolone has shown that promising compounds can still fail in phase III trials.
Calcification tendency and graft failure
As a result of CKD, the kidney loses its ability to excrete phosphate, leading to an increase in serum phosphate concentration. As a consequence, the tendency to calcification increases in other organs and in the connective tissue, especially in the vessels. This calcification is not a passive process that depends only on phosphate concentration, but is inhibited or promoted by various regulators. The activity of the regulators is probably also responsible for the fact that the tendency to calcification varies among patients.
A new test that determines the propensity to calcify has also been shown to increase mortality in patients with kidney disease [5,6]. A new study has now investigated the association of calciphylaxis propensity, mortality, and graft failure in patients undergoing renal transplantation [7].
The study enrolled 699 kidney transplant patients. Calcification propensity was measured at a mean of 5.4 years after transplantation. During the follow-up of 3.1 (2.7-3.9) years, 81 (12%) of the patients died and graft failure developed in 45 (6%). The higher a patient’s propensity for calcification, the greater his or her risk for graft failure or death.
What treatment for secondary hyperparathyroidism?
Secondary hyperparathyroidism (sHPT) occurs in more than 90% of patients with severe renal failure [8]. Most common consequences of sHPT are osteodystrophy with bone pain and cardiovascular complications. For a long time, parathyroidectomy and the administration of vitamin D were the only therapeutic options. The parathyroid hormone inhibitor cinacalcet, which increases the sensitivity of calcium receptors in the parathyroid glands and thereby inhibits the excessive production of parathyroid hormone, has now been on the market for several years.
The COSMOS study (“Current management of sHPT: a multicentre observational study”) prospectively evaluated the two treatment modalities parathyroidectomy vs. cinacalcet treatment in 6251 hemodialysis patients [9]. Cinacalcet treatment was found to be associated with longer survival; additive administration of vitamin D further improved patient benefit. The authors advocate conducting a randomized controlled trial to determine whether surgical or drug therapy provides greater benefit to the patient in sHPT.
Peritoneal dialysis: What to do in case of infections?
Catheter exit infections (IKA) are one of the most common complications in peritoneal dialysis (PD). Early diagnosis is tremendously important to prevent catheter removal if possible. Surgical technique, postoperative procedure, and wound care play key roles in the prevention of IKA. The aim of the presented study was to investigate the incidence as well as the outcome of IKA with different treatment approaches [10].
Dialysis catheters were implanted in 130 consecutive patients, 37 of whom were women, using a standard surgical method. The average age was 63.7 years (range: 25-88). All patients received preoperative antibiotic prophylaxis of 1 g cephazolin i.m.. The mean duration of PD was 24 months in the study patients. If IKA occurred, it was treated according to international guidelines.
During the observation period (12 months per catheter), 52 IKA occurred, equivalent to one IKA per 67 patient-months. The incidence of IKA was 0.18 per person-year. The most common causative germs were Staphilococcus aureus (50%), Staphilococcus epidermidis (16%), and Pseudomonas (16%). Antibiotic treatment was given to 34 cases of IKA, resulting in success in 26 patients (77%). In 18 patients, cuff shaving (surgical removal of infected tissue after ultrasound examination) was performed as initial therapy, which was successful in 14 (78%) of patients. In eight patients in whom primary antibiotic therapy had not worked, cuff shaving was subsequently performed, which cured the infection in two patients. In five patients in whom both treatment procedures had failed, the catheter was removed and reimplanted, and five additional patients were assigned to hemodialysis after catheter removal.
The study shows that antibiotic therapy leads to cure of the infection in the majority of cases. Conservative surgical therapy (cuff shaving) produces significantly better results when performed as the primary treatment after evaluation with ultrasound. Overall, the rate of catheter removal was low (18%).
Source: ERA-EDTA Congress (European Renal Association and European Dialysis and Transplant Association), May 31-June 3, 2014, Amsterdam.
Literature:
- Pergola PE, et al: Bardoxolone methyl and kidney function in CKD with type 2 diabetes. NEJM 2011; 365: 327-336.
- De Zeeuw D, et al: Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. NEJM 2013; 369: 2492-2503.
- Meyer C, et al: Investigation of serious adverse events in bardoxolone methyl patients in BEACON. Abstract 4074.
- Haller H, et al: CCL2 inhibition with emapticap pegol (nox-E36) in type 2 diabetes patients with albuminuria. Abstract 4079.
- Pasch A, et al: Nanoparticle-based test measures overall prospensity for calcification in serum. J Am Soc Nephrol 2012; 23: 1744-1752.
- Smith, et al: Serum calcification propensity predicts all-cause mortality in predialysis CKD. J Am Soc Nephrol 2014; 25: 339-348.
- Keyzer CA, et al: High serum calcification propensity is associated with mortality and graft failure in renal transplant recipients. Abstract 4064.
- Klempa I: Treatment of secondary and tertiary hyperparathyroidism – surgical viewpoints. Surgeon 1999; 70: 1089-1101.
- Cannata-Andia JB, et al: Impact of parathyroidectomy and cinacalcet use on survival in chronic hemodialysis patients: the COSMOS study. Abstract 4063.
- Ancarani P, et al: Exit site infection in peritoneal dialysis: surgical conservative therapy is better? Abstract SP499.
CONGRESS SPECIAL 2014; 5(2): 33-35
