As with all extracorporeal blood-purification procedures (meaning that they take place outside the human body), dialysis is associated with certain risks for the patient that in the worst case can even lead to death. National as well as international standards and laws therefore stipulate binding safety standards for dialysis products. Beyond that, we have created our own quality guidelines for research and development that partly exceed the legal requirements. It is also important to train the nursing staff as well as the patients themselves to ensure that every treatment is as safe and gentle as possible. In addition, Fresenius Medical Care develops procedures and devices as part of a continuous product improvement process to minimize as far as possible the risk that patients may suffer harm due to a technical error or human failure.

A rare but particularly dangerous incident is the loss of bloodBloodFluid circulating in the body composed of plasma and cells (red blood cells, white blood cells, platelets, etc.). The main function of blood is to transport oxygen, nutrients and hormones to the cells and to remove waste products (such as carbon dioxide and urea). Blood also regulates the water and electrolyte balance and helps fight off contaminants as part of the immune system. during dialysis – for example due to a leak in the bloodline system or the fixture of the venous needle, which connects the patient’s vascular access with the bloodline system, coming loose. Blood loss can then occur immediately and lead to death within a very short time. This risk is particularly high when dialysis is unsupervised, for example during treatment at home or overnight – both methods that in principle are particularly compatible for many patients and that produce very good results. Dialysis machines do have an integrated alarm function – they continuously measure the pressure in the extracorporeal system, i.e. the cycle outside of the patient’s body, and respond with an alarm if the pressure drops sharply, causing the blood pump to stop and the venous clamp to close so that no more blood can leave the patient’s body. However, so far the measurement technology in standard dialysis machines is not capable of reliably recognizing all the potential causes of blood loss and reacting quickly enough. After all, the difference in pressure can be minimal, comparable to the drop in pressure caused by the patient coughing or slightly changing the position of his arm. If the standard measurement technology of the device was sensitive to this distinction, the result would be constant false alarms, which would prevent effective treatment, make the patient very anxious, and possibly even result in the nursing staff stopping to pay attention after a while.

For this reason, the dialysis industry has been working for many years on developing systems to protect patients better from blood loss. One example is the wetness detector, a sensor that reacts to moisture, which we also use in our own dialysis clinics. However, in order to react, the device must be positioned directly where the blood is leaking. Fresenius Medical Care is therefore currently working on a new safety system based on innovative software: Venous Needle Disconnect (VND). The system is capable of intelligently analyzing extracorporeal pressure signals: It is able to recognize common disturbances as such and reacts to potentially dangerous, subtle pressure irregularities – for example caused by a needle slipping, or by leaking or bent bloodline sections – and responds with an alarm that activates the necessary safety reactions of the dialysis machine. We intensively tested the VND system in 2010 and intend to integrate it into the monitor of our dialysis devices of the 4008 and 5008 series, for both home as well as clinical use, as of the current business year. Although the risk of a blood loss cannot be completely avoided even with VND, we are convinced that the new system offers a particularly reliable technology for which there is no comparable alternative in the dialysis market to date.

For many years, cardiac and vascular diseases have been one of the most frequent causes of death for dialysis patients in all age groups. The primary trigger was generally thought to be permanent fluid overload. This is typical for chronic kidney failureChronic kidney failure (end-stage renal disease, ESRD)Permanent failure of the kidney (terminal kidney failure) resulting from slow and progressive loss of the kidney function over several years. Since the renal function cannot be recovered, the patient has to be treated with renal replacement therapy, i.e. kidney transplantation or dialysis. Chronic kidney failure is accompanied by long-term complications such as renal anemia, hypertension and other cardiovascular problems, as well as bone disease, loss of appetite and malnutrition., because the body is no longer able to naturally excrete excess fluid. However, it used to be difficult to precisely determine to what extent a patient was overhydrated – until Fresenius Medical Care developed the Body Composition MonitorBCM – Body Composition MonitorThis device can be used to determine the exact makeup of the human body and its fluids (body water, fat, and fat-free body mass) and to quantify the level of overhydration in dialysis patients. (BCM). This device is capable of precisely measuring the composition of the human body and its fluid status. Thanks to the BCM – together with the analysis procedure developed by Fresenius Medical Care – it is finally possible to conclusively and methodically demonstrate that once it reaches a certain level, fluid overload represents a significant mortality risk, and that correcting this condition can significantly increase the patient’s life expectancy.

Since we first launched the BCM in 2007, both our own and external research on and with this diagnostic tool have advanced significantly. Confirming general expectations, studies carried out in the meantime have demonstrated that a significant number of hemodialysisHemodialysis (HD)Treatment method for chronic kidney failure where the patient’s blood flows outside the body through disposable bloodlines into a special filter, the dialyzer. The dialysis solution carries away waste products and excess water, and the cleaned blood is returned to the patient. The process is controlled by a hemodialysis machine that pumps blood, adds anticoagulants, regulates the purification process, and controls the mixing of the dialysis solution and its flow rate through the system. A patient typically receives three treatments per week, lasting from three to six hours each.
patients (around 25%) have permanent fluid overload at a critical level. With the help of the BCM, it is now possible to identify atrisk patients, who would otherwise be completely unremarkable from a clinical aspect. A new finding presented by both our own and external researchers at expert symposiums and in scientific publications in the reporting year concerns peritoneal dialysisPeritoneal Dialysis (PD)Dialysis treatment method using the patient’s peritoneum, i.e. the tissue that covers the inner surface of the abdominal cavity and the abdominal organs, as the dialyzing membrane for blood purification. A sterile dialysis solution is introduced and removed through a catheter that has been surgically implanted into the patient’s abdominal cavity. The solution absorbs toxins and excess water. Most treatments are supported by a machine, the cycler, and are administered by the patients in their home or workplace several times a day or during the night.
(PD) patients. Previously, it was assumed that PD patients suffer from fluid overload less often, but without the evidence of clinical data that would have held up under scrutiny. Thanks to the BCM, it has now been proven that there are even more “hidden”, in other words clinically unremarkable at-risk patients in the PD population than there are with hemodialysis.

A study published last year by an international team of Fresenius Medical Care researchers confirms that the BCM provides medical staff with an objective benchmark for a patient’s fluid levels, and that the fluid overload, and thus hypertension, can be reduced by means of a corresponding therapy. In turn, for patients with a low fluid volume, the BCM diagnosis helped to reduce specific complications during dialysis. Another connection that is becoming increasingly obvious in our work with the BCM: Fluid overload can diminish the efficacy of medication administered to combat the concomitant diseases of kidney failure – a critical insight for attending physicians.

Based on these clear results, the BCM is gaining significance at Fresenius Medical Care as an instrument for controlling the fluid levels in patients with chronic and acute kidney failure, and therefore also for detecting and treating concomitant symptoms. For example, in the year under review we integrated this diagnostic device into PatientOnline, our data management system for PD patients. This means that BCM data can be imported directly into the data management system for PD treatment and directly influence the calculation of the correct dialysis dose.

As we mentioned in the 2009 annual report, an interregional team of experts at Fresenius Medical Care has been working for several years on the development of a wearable artificial kidney – a dialysis device that is so small and light that patients can wear it directly on their body. It is particularly similar to a real kidney and its natural function as it is continuously in operation. We see great potential in the long term for such a device, not only because a wearable kidney would grant the patient much more freedom and mobility: Since the bloodBloodFluid circulating in the body composed of plasma and cells (red blood cells, white blood cells, platelets, etc.). The main function of blood is to transport oxygen, nutrients and hormones to the cells and to remove waste products (such as carbon dioxide and urea). Blood also regulates the water and electrolyte balance and helps fight off contaminants as part of the immune system. is continuously being cleansed, this procedure also promises to deliver good results. In addition, in light of the steadily growing number of patients, it can help to solve the problem of limited capacity in clinics in the long term and allow more patients to be treated in a cost effective manner

The idea of a wearable device for dialysis is not new: Scientists have been working on it for almost 40 years, but so far without marketable success. We believe that the system we are currently working on is the first real chance in many years to achieve a true breakthrough in the treatment of patients with chronic kidney failure. Our many years of technological experience and expertise give us a clear advantage in developing this device and are in our opinion crucial for finding a marketable solution. We have consolidated our expertise through acquisitions: After purchasing the U.S. company Renal Solutions Inc. in 2007 – a specialist in the recycling of used dialysate through sorbents, which plays a crucial role in decreasing the size of dialysis machines (see following paragraph) – we acquired the California-based medical technology company Xcorporeal in the reporting year; this company is working on promising sorbent-based solutions for mobile and wearable dialysis machines for clinical and home use.

A wearable system must work with far less dialysis solution than standard peritoneal or hemodialysis procedures. The challenge is therefore to reduce the quantity of dialysis solution from 175 to 360 liters per week at present (depending on the procedure), to approximately 150 to 500 milliliters of solution that circulate inside the device and can be reprocessed repeatedly. This recycling is performed by the sorbent substances mentioned above that effectively bind the toxic agents and waste product in the solution (adsorption). However, one notable exception is urea: Up to now, no sorbent has been able to bind it with satisfactory results. To effectively remove urea from used dialysis solution, Fresenius Medical Care has developed an innovative hollow fiber membrane. It consists of two layers with a structure and composition that actively help to transport substances: The membrane’s functional coating enables urea to be transported out of the dialysis solution, while retaining the electrolytes that are crucial for survival. The urea is chemically split by an enzyme in the outer part of the hollow fiber. The ammonium released by this process is bound by sorbents; any residual toxic ammonium is unable to reinfiltrate the dialysis solution.

The development of the multi-layered functional membrane was made possible by our decades of experience in the production of polysulfone membranes. Fresenius Medical Care developed this particularly high-performing and blood-compatible type of membrane and has used it as a core element in its dialyzers since the 1980s in a continuously improved form. The material has since become established as a valuable worldwide therapy standard in blood purification procedures. The new, multi-layered membrane is based on an innovative micromechanical silicon-based technology. This technology is used to produce the microscopic spinning nozzles required for processing several membrane materials, including polysulfone, in several layers at the same time. We have already filed a number of patent applications for the complex design of these nozzles.

The first practical result of the new spinning process is a dual-layered urea membrane that we now intend to further optimize for use in a wearable artificial kidney. But in principle, the technology is interesting for all sorbent-based dialysis devices that rely on the dialysis solution being recycled, so that ultimately patients outside of clinics can be treated more flexibly.

We want to offer patients in our own clinics and our customers’ patients top quality at an affordable price. One approach we are pursuing more and more to increase quality and cost efficiency in equal measure is to offer integrated therapy systems and software solutions. By bundling products in this way, it is possible to improve therapeutic performance on the one hand and to record and monitor it better on the other. This should not only result in higher treatment quality, but also a more efficient use of personnel as well as medical and financial resources. More information about the growing demand for integrated services can be found in the “Opportunities” section.

One example of such a therapy system is our new 2008T hemodialysis machine, which we developed for the U.S. market in close collaboration with the Renal Research Institute (RRI) see here. Following approval by the FDAFDAThe U.S. Food and Drug Administration. (American Food and Drug Administration), we launched the device in November 2010, on the occasion of the ASN Renal Week (American Society of Nephrology), the most important industry sector conference in the U.S. The 2008T has already proven a success: We received numerous orders even prior to introducing it on the market.

The 2008T is the first approved hemodialysis machine on the U.S. market with an integrated software platform for entering and managing clinical treatment data directly at the treatment couch. The new module is designed to assist physicians and clinic staff in efficiently and promptly recording the data required by the authorities for billing services pursuant to the new reimbursement system; see “Health and reimbursement systems” section. In addition, it is supposed to generally help simplify the daily clinic routines and further improve clinical data and quality management. The 2008T can be connected to various data management systems used in U.S. dialysis clinics, making it particularly flexible. Several providers of dialysis-related software have already had their software certified for use with the new device. In addition, we are currently testing an integrated infusion pump for intravenously administered iron compounds developed specifically by us for the 2008T and already approved by the FDA. This pump is designed to make it easier for clinic staff to dose and administer the iron exactly, thereby further increasing patient safety. We intend to start marketing the new module this year.

In the International segment, we worked on further developing our software and service offer for clinical data management, the TDMS (Therapy Data Management System), in the year under review. Here, too, the trend is toward integrated system solutions that can capture all routine clinical procedures, from the treatment data of individual dialysis or diagnostic devices up to the central medical data management system. In this way, the system solutions help to make processes more efficient, increase data quality and continuously improve the quality of treatment. In 2010, we coordinated the various products in the TDMS even more closely to better support the nursing staff in dialysis clinics.

One example is the dataXchange panel (dXp), a software platform for managing treatment data. It is integrated into the monitor of our 5008 series hemodialysis machine and was introduced to the market in 2007. We significantly enhanced the functions of the dXp in 2010 so that it now captures all the steps required for dialysis treatment and displays them on the 5008 dialysis system monitor. This includes calculating excess fluid in the patient’s body based on his weight; this data is required to individually adjust the dialysis dosage. Apart from the patient’s weight prior to treatment, the calculation includes the amount of fluids the patient will consume in the form of beverages during several hours of treatment. In addition, the dXp captures the patient’s individual treatment settings, i.e. clinical quality goals such as target Kt/VKT / VIndicator to evaluate treatment quality. It is calculated by dividing the product of urea clearance (K) and the length of treatment (dialysis time, t) by the filtration rate of certain toxins (the urea distribution volume in the patient, v). values ( see here), the duration of each dialysis session as well as the treatment parameters prescribed by the patient’s physician, for example the blood flow in milliliters per minute or the composition of the dialysis solution. The new dXp stores not only the patient’s drug regimen, but also the exact specifications of the consumables used during the patient’s dialysis, for example the type of dialyzerDialyzerSpecial filter used in hemodialysis for removing toxic substances, waste products of metabolic processes and excess water from the blood. The dialyzer is sometimes referred to as the “artificial kidney”. or the selected dialysis concentrate. Last but not least, the panel now also indicates if the dialyzer was disinfected after treatment – providing the nursing staff with valuable assistance and an additional tool to increase patient safety. These improvements significantly strengthen the role of the dXp as an efficient data interface between the treatment couch and the clinic’s central quality management data system.

In the year under review, we also enhanced the medical data management system PatientOnline as an integrated solution in the peritoneal dialysis sector. For the first time, it is now available not only for individual users – usually the attending physician – but for several trained users, as a joint data base. The new version of PatientOnline is currently undergoing field testing; we plan to introduce it in 2011.

In addition to developing innovative products and procedures as well as enhancing existing ones, known as sustaining engineering, our employees also carry out clinical research on chronic kidney failure, dialysis and technologically related blood-purification procedures. For example, in 2010 we presented the results of a study that was one of only a few scientific publications to deliver first meaningful data on blood purification treatment for patients with liver cirrhosis and a rapid drop in their liver function. The study examined the effectiveness of treating this serious illness with the Fresenius Medical Care Prometheus system compared to purely standard therapy, with the following results: Although Prometheus did not lead to a higher patient survival rate overall, for certain patient groups – namely patients with a particularly severe limitation of liver function as well as patients who also suffered from kidney failure – Prometheus increased the survival rate by 36% compared to standard treatment.

Even though the difference compared to standard treatment was not considerable for all groups, the results of the study are important for Fresenius Medical Care: The study shows that with certain symptoms, detoxification with Prometheus can significantly contribute to stabilizing patients long enough for their liver to regenerate or to perform a life-saving liver transplant. Considering that this discipline is still at an early stage, this is an important signal that our research and development is on the right track. We will continue to pursue this path over the next few years, internally as well as with external partners, to gradually improve the situation for patients with what continues to be an almost untreatable, life-threatening illness.