Klinikum Coburg

Coburg, Germany

Klinikum Coburg

Coburg, Germany
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Brandenburg V.M.,RWTH Aachen | Sinha S.,Foundation Medicine | Specht P.,RWTH Aachen | Ketteler M.,Klinikum Coburg
Pediatric Nephrology | Year: 2014

Calciphylaxis [calcific uraemic arteriolopathy (CUA)] is a rare disease at the interface of nephrology, dermatology and cardiology. CUA most often occurs in adult dialysis patients. It is only rarely seen in patients without relevant chronic kidney disease, and only anecdotal reports about childhood calciphylaxis have been published. Clinically, CUA is characterized by a typical cascade, starting with severe pain in initially often inconspicuous skin areas, followed by progressive cutaneous lesions that may develop into deep tissue ulcerations. The typical picture is a mixture of large retiform ulceration with thick eschar surrounded by violaceous, indurated, tender plaques. The histopathological picture reveals arteriolar, often circumferential, calcification and extensive matrix remodelling of the subcutis. These findings explain the macroscopic correlation between skin induration and ulceration. The prognosis in CUA patients is limited due to underlying comorbidities such as uraemic cardiovascular disease and infectious complications. The etiology of CUA is multifactorial, and imbalances between pro- and anti-calcification factors, especially in the setting of end-stage renal disease play an outstanding role. Oral anticoagulant treatment with vitamin K antagonists is a predominant CUA trigger factor. It is speculative as to why children and adolescents only develop calciphylaxis in exceptional cases, although a seldom usage of vitamin K antagonists and the preserved mineral buffering capacity of the growing skeleton may be protective. © 2014 IPNA.


Cozzolino M.,University of Milan | Ketteler M.,Klinikum Coburg | Zehnder D.,Warwick Medical School
European Journal of Heart Failure | Year: 2010

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25-dihydroxyvitamin D) by the 25-hydroxy vitamin D 1-hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin-angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD-MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD-MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients. © 2010 The Author.


Brandenburg V.M.,RWTH Aachen | Cozzolino M.,University of Milan | Ketteler M.,Klinikum Coburg
Journal of Nephrology | Year: 2011

Introduction: Calcific uremic arteriolopathy (CUA), also known as calciphylaxis, is a rare disease most frequently occurring in patients with advanced chronic kidney disease (CKD). The clinical picture is typically characterized by very painful skin lesions and ulcerations following calcification and occlusion of small cutaneous arterioles. CUA is life-threatening due to infections and concomitant cardiovascular diseases. Methods: We performed a literature search for the terms calciphylaxis and calcific uremic arteriolopathy and summarized current state-of-the-art knowledge about pathophysiology, clinical picture, course of the disease, as well as treatment options. We have filled out the literature data with our personal treatment experiences. Results: A combination of various local and systemic risk factors are necessary to cause the development of calciphylaxis. This pathophysiological cascade is still incompletely understood. Patients with advanced CKD and dialysis patients are especially at risk to develop CUA. Regarding therapy, no randomized prospective trials are available, and treatment is rather based on pathophysiological considerations as well as on evidence derived from case reports or case series. Therapy focuses on optimized dialysis treatment, control of chronic kidney disease-mineral and bone disorder parameters, experimental anticalcification strategies and wound care. Conclusion: Facing the still deleterious outcome of patients with calciphylaxis, further studies on prophylaxis as well as treatment are urgently needed. Current treatment strategies may help ameliorate the course of the disease in some patients. However, it is still unclear if they are able to decrease mortality. © 2011 Società Italiana di Nefrologia.


Biggar P.,Klinikum Coburg | Ketteler M.,Klinikum Coburg
Expert Opinion on Pharmacotherapy | Year: 2010

Importance of the field: Altered mineral metabolism in chronic kidney disease (CKD) is associated with increased morbidity, mortality, hospitalization, cost of care and reduced quality of life. Phosphorus control, one component of CKD metabolic derangements, is potentially related to impaired outcomes and has significant room for improvement. Areas covered in this review: Historical, present and future aspects of treatment of hyperphosphatemia focusing on sevelamer hydrochloride and sevelamer carbonate. What the reader will gain: Comprehensive insight into the background and controversies regarding phosphate binders. Take home message: While calcium-free phosphate binders with a sevelamer backbone may offer therapeutic advantages for CKD patients at risk, more studies comprising significant patient numbers are warranted to answer compelling clinical questions. © 2010 Informa UK, Ltd.


Strohmaier W.L.,Klinikum Coburg | Wrobel B.M.,Klinikum Coburg | Schubert G.,Urinary Stone Laboratory
Urological Research | Year: 2012

Overweight, arterial hypertension and disturbances of the carbohydrate metabolism are important parameters of the metabolic syndrome (MS). The most important factor regarding renal pathophysiology is insulin resistance resulting in alterations of urine acidification and low urine pH. Since low urine pH is the main risk factor for uric acid urolithiasis (UAU), UAU may be regarded as a renal manifestation of the MS. So far, there are only few data on the prevalence of parameters of the MS in UAU patients especially with regard to the severity of the disease and recurrence rate, respectively. The objective of this study was to know more about the prevalence of different parameters of the MS and their importance for the natural history of this type of renal stone disease using a total number of 167 consecutive patients with pure UA stones. Stone analysis was performed by polarization microscopy and X-ray diffraction. The following parameters were measured: age, sex, systolic and diastolic arterial blood pressure (RRs and RRd), number of stone episodes, diabetes mellitus (DM); serum: creatinine, calcium, sodium, potassium, uric acid, glucose; urine: pH-profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. The following results were obtained (means ± standard deviations): age 61 ± 13 years, BMI 30 ± 6 kg/m2, BP 147/84 ± 22/13 mmHg, number of stone episodes 1.8 ± 1.2, DM 32%; serum: creatinine 1.3 ± 0.6 mg/dl, glucose 136 ± 52 mg/dl, UA 6.3 ± 1.8 mg/dl, calcium 2.4 ± 1.3 mmol/l, sodium 134 ± 18 mmol/l, potassium 4.1 ± 0.4 mmol/l; urine: pH 5.87 ± 0.27, volume 2.4 ± 1.1 l/d, calcium 3.5 ± 2.5 mmol/d, UA 3.9 ± 2.4 mmol/d, citrate 1.3 ± 1.1 mmol/d, ammonia 41 ± 26 mmol/d, urea 390 ± 176 mmol/d. A significant positive correlation could be found for BMI and urea excretion, BMI correlated negatively with RRs and RRd. There was no significant correlation between BMI, urine pH, citrate, ammonia and UA in serum and urine. Undue acidity and hyperuricosuria were found in two-thirds of the UAU patients, increased urea excretion and decreased excretion of ammonia in less than 25%, Hyperuricemia in 37%. There was no significant correlation between the number of stone episodes and any other parameter studied. Overweight, arterial hypertension and DM as parameters of the MS are frequent in many patients with UAU. However, these parameters do explain the pathogenesis in two-thirds of the patients. The severity of the disease and the recurrence are not influenced by the presence of these metabolic parameters. Therefore, MS is no prognostic factor in UAU. © Springer-Verlag 2011.


Brandenburg V.M.,RWTH Aachen | Ketteler M.,Klinikum Coburg | Rodriguez M.,Hospital Universitario Reina Sofia Cordoba
Kidney International Supplements | Year: 2011

Accelerated vascular calcification is a hallmark of patients with chronic kidney disease (CKD) and contributes substantially to the enormous disease burden and high mortality in these patients. Within the last 10 years, many authors have significantly contributed to the progress that has been made in our understanding of how important the problem of vascular calcification is for CKD and end-stage renal disease patients. In parallel, our knowledge has substantially increased about the pathophysiology of vascular disease. In consequence, dialysis patient care has undergone significant changes in the last decade. Our review focuses on publications on vascular health in uremia during the period 2000-2010, and we have chosen 20 landmark publications out of this decade that help us to summarize the increasing knowledge on this issue. Two guidelines (Kidney Disease Outcomes Quality Initiative 2003 and Kidney Disease: Improving Global Outcomes 2009) have been published with a strong focus upon bone, mineral, and cardiovascular disorders. These 20 publications highlight in a chronological step-by-step approach the developments and progress that have been made in the field of 'vascular calcification in uremia'. This subjective review of selected contributions attempts to bridge the gap from basic science data about the role of phosphate, Klotho, and vitamin D to vascular wall biology, and integrates clinical and epidemiological data, which have substantially influenced CKD patient care regarding vascular health.


Biggar P.H.,Klinikum Coburg | Ketteler M.,Klinikum Coburg
Clinical Nephrology | Year: 2013

The development of ESAs (Erythropoiesis Stimulating Agents) revolutionized the treatment of renal anemia. However, the initial euphoria has abated and, in the last few years, studies have shown that ESAs should not be administered without caution as the rate of cardiovascular events and possibly tumor related deaths may increase with over-augmented hemoglobin levels. Renal anemia therapy is discussed against the background of recent decisions to lower the recommended hemoglobin target ranges in chronic kidney disease (CKD) patients on ESAs, thus, necessitating a redefinition of treatment quality criteria and exposing areas requiring further research. © 2013 Dustri-Verlag Dr. K. Feistle.


Jahnen-Dechent W.,RWTH Aachen | Ketteler M.,Klinikum Coburg
CKJ: Clinical Kidney Journal | Year: 2012

As a cofactor in numerous enzymatic reactions, magnesium fulfils various intracellular physiological functions. Thus, imbalance in magnesium status - primarily hypomagnesaemia as it is seen more often than hypermagnesaemia - might result in unwanted neuromuscular, cardiac or nervous disorders. Measuring total serum magnesium is a feasible and affordable way to monitor changes in magnesium status, although it does not necessarily reflect total body magnesium content. The following review focuses on the natural occurrence of magnesium and its physiological function. The absorption and excretion of magnesium as well as hypo- and hypermagnesaemia will be addressed. © The Author 2012.


Liangos O.,Klinikum Coburg
Minerva Urologica e Nefrologica | Year: 2012

Acute kidney injury is a common complication in hospitalized patients and is associated with substantially increased morbidity and mortality. Frequently, it is caused by impaired renal perfusion, ischemia and reperfusion injury, sepsis or urinary tract obstruction, but often its etiology is multifactorial. In this context, the contribution of nephrotoxic medications to the development of AKI plays an important role. This review begins with an attempt to evaluate the importance of drug-related acute kidney injury in general. Then, a selected list of 7 classes of drugs or compounds, namely aminoglycosides, aristolochic acid, cytostatic drugs, nonsteroidal anti-inflammatory drugs, osmotic agents, radiocontrast, and phosphate salts are discussed in depth, including their epidemiology, pathophysiology, clinical features and treatment. While not attempting to be exhaustive, this review attempts to provide an overview with additional in-depth information on certain classes of drugs that are either of general importance or have recently emerged in the literature.


Ketteler M.,Klinikum Coburg
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2012

Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT. Patients aged ≥18 years with Stage 5 chronic kidney disease receiving maintenance haemodialysis and with intact parathyroid hormone (iPTH) 300-800 pg/mL, calcium 8.4-10.0 mg/dL (2.09-2.49 mmol/L) and phosphorus ≤6.5 mg/dL (2.09 mmol/L) were randomized within two strata defined by the mode of paricalcitol administration to treatment with paricalcitol- (intra-venous, US and Russian sites, IV stratum; oral, non-US and non-Russian sites, oral stratum) or cinacalcet-centred therapy. The primary endpoint is the proportion of patients in each treatment group who achieve a mean iPTH value of 150-300 pg/mL during Weeks 21-28 of treatment. Assuming efficacy response rates of 36 and 66% for cinacalcet and paricalcitol, respectively, and a 20% discontinuation rate, 124 subjects in each stratum were estimated to provide 81% power to detect a 30% absolute difference in the primary endpoint. Of 746 patients screened, 272 (mean age, 63 years; mean iPTH, 509 pg/mL) were randomized. Mean duration of haemodialysis at baseline was 3.7 years. Comorbidities included hypertension (90.4%), Type 2 diabetes (40.4%), congestive heart failure (17.3%), coronary artery disease (34.6%) and gastrointestinal disorders (75%). The study participants are representative of a multinational cohort of patients on haemodialysis with elevated iPTH. The study results will provide valuable information on the best available treatment of SHPT in patients on haemodialysis.

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