[Anticoagulation in patients with chronic kidney disease : Recommendations from the working group "Heart-Kidney" of the German Cardiac Society and the German Society of Nephrology]. / Antikoagulation bei Patienten mit chronischer Niereninsuffizienz : Empfehlungen der Arbeitsgemeinschaft "Herz ­ Niere" der Deutschen Gesellschaft für Kardiologie ­ Herz- und Kreislaufforschung und der Deutschen Gesellschaft für Nephrologie.

Indications for anticoagulation are thromboembolic events, prosthetic heart valves, and atrial fibrillation with a corresponding risk score. Clinical trials have excluded patients with advanced chronic kidney disease and these data cannot be always generalized to patients with chronic kidney disease. Non-vitamin K antagonist oral anticoagulants (NOACs) are mostly not recommended or are contraindicated in advanced stages of chronic kidney disease. Observational studies have shown that dialysis patients with atrial fibrillation do not profit from coumarin anticoagulants; prospective studies are lacking.

Simple technique of repair for Barlow syndrome with posterior resection and chordal transfer via minimally invasive approach: primary experience in a consecutive series of 22 patients.

OBJECTIVE: Current techniques for mitral valve repair (MVR) in Barlow's disease require high level of surgical expertise due to a complex anatomy. A novel and simple standardized technique that particularly considers the pathological changes of the mitral valve in Barlow's disease has been developed. METHODS: Between 2009 and 2013, 22 patients underwent minimally invasive MVR for Barlow's disease and severe mitral regurgitation (MR). A simple, standardized technique was applied, including resection of P2 segment of posterior mitral leaflet (PML) with preservation of the shortest chordae, transfer of the preserved chordae to A2, and implantation of a semi-rigid open ring. In 2015, all patients were contacted for follow-up by transthoracic echocardiography (TTE) and interviewed for their clinical status. RESULTS: During follow-up (mean 2.8 ± 1.1 years; 100% complete), one patient died due to abdominal bleeding 4 months after the initial MVR and one patient with severe calcification of PML underwent valve replacement due to recurrence of MR. Among the remaining cohort (mean follow-up 3.0 ± 1.0 years), NYHA class I, II and III was present in 13, 6, and 1, respectively. TTE demonstrated MR grade 0, 1+, or 2+ in 40, 55, and 5%, respectively, with mean and maximum transvalvular gradients ranging at 1.9 ± 1.7 and 4.7 ± 3.3 mmHg, respectively. CONCLUSIONS: A simple and standardized technique facilitates the repair of MR in the presence of Barlow's, simultaneously addressing the height of PML and the position of the anterior leaflet. This technique has proven durable in the mid-term follow-up in our small series and warrants further validation in larger cohorts.

Effects of an increase in time vs. frequency on cardiovascular parameters in chronic hemodialysis patients.

UNLABELLED: Cardiovascular mortality is still high and many risk factors are inadequately controlled in patients on conventional chronic hemodialysis. Recent studies on intensified treatment schedules by either increasing length or frequency of dialysis sessions have shown promising results with better control of blood pressure, reduction of left ventricular hypertrophy and easier control of calcium/phosphate metabolism. AIM: The present observational study compared the effect of different forms of "intensified dialysis treatment" i.e. either long nightly intermittent (LNHD, 3 x 7.5 - 8 h) or short daily dialysis sessions (DHD, 6 x 2.5 - 3 h) on cardiovascular parameters, phosphate and anemia control in comparison to standard treatment schedules (SHD, 3 x 4 - 5 h). METHODS: All patients stable on hemodialysis between 18 and 80 years of age and with either uncontrolled hypertension and/or left ventricular hypertrophy and/or frequent intradialytic hypotension, were asked to participate in intensified dialysis therapy by either LNHD or DHD. Patients not willing to change their dialysis regime were asked to participate as control group (SHD). Primary end point was 24-h ambulatory blood pressure, secondary end points were predialysis blood pressure, left ventricular mass index (LVMI) and fractional shortening (FS), control of calcium, phosphate and anemia. Patients were followed up for 1 year. RESULTS: 17 patients opted for LNHD, 8 for DHD, 19 patients served as control group. After 1 year of treatment 24-h blood pressure was unchanged in all groups. Predialysis systolic blood pressure decreased in LNHD and DHD, but increased in SHD. Mean LVMI decreased in all treatment groups (DHD -20.1 +/- 24.0%, SHD -13.6 +/- 33.4%, LNHD -6.1 +/- 32.2%). The mean number of antihypertensive tablets/day was reduced in DHD by 3.3 tablet units, in LNHD by 1.2 tablet units, but increased in SHD patients. FS improved in patients on LNHD and DHD, but decreased in patients on SHD. Regression of LVMI was independent of dry weight which was unchanged in LNHD and SHD but increased in DHD. In contrast to SHD, phosphate control and Ca x P product improved in DHD and LNHD with less phosphate binding tablets. Intact PTH did not change in SHD, but decreased in DHD and LNHD. Hemoglobin increased in groups on intensified treatments, but fell in SHD. EPO resistance index fell in LNHD, but increased in DHD and SHD. CONCLUSION: While reduction in 24-h blood pressure was not achieved by intensified dialysis, both schedules showed favourable effects on LVMI and FS with less antihypertensive medication. This was independent of reduction in dry weight. These effects were more pronounced in DHD patients. In contrast, in SHD patients, stable 24-h blood pressure and reduction in LVMI were achieved on the expense of an increasing amount of antihypertensive medication and with worsening of FS.

Insulin-like growth factor 1 and 2 serum concentrations in dialysis patients with secondary hyperparathyroidism and adynamic bone disease.

BACKGROUND: Insulin-like growth factor-1 and -2 exert well characterized effects on bone metabolism via paracrine and endocrine pathways. However, the role of circulating levels of IGFs and their binding proteins (IGFBP) in renal bone disease is still controversial. PATIENTS AND METHODS: To investigate whether circulating IGFs play a role in the pathogenesis of different forms of renal bone disease, we performed a cross sectional study in 38 stable dialysis patients (32 hemodialysis, 6 peritoneal dialysis). Patients were selected for the type of bone disease according to biochemical bone markers and bone histology. 25 Patients had adynamic bone disease (ABD; defined by plasma iPTH < 1,5 fold the upper limit of normal). Thirteen patients had secondary hyperparathyroidism (sHPT; defined by plasma iPTH > 10 fold the upper limit of normal). Serological diagnosis was confirmed in a subgroup of patients by bone histology (12 patients with type IIa according to Delling, ABD; 9 patients with type IIIb according to Delling, sHPT). Patients with signs or symptoms of aluminum toxicity were excluded from the study. RESULTS: Serum IGF-1 and -2 concentrations were comparable in both groups and were within the reported normal range for an age matched healthy control population. They did not correlate with biochemical markers (iPTH, bAP, osteocalcin) or histological manifestations of renal bone disease. Furthermore, semiquantitative analysis of IGFBP-2 and -3 carried out in patients with bone biopsies did not correlate with biochemical markers or histological indices of renal bone disease. CONCLUSION: In conclusion, in contrast to previous reports, the present data do not confirm a correlation between serological or histological markers of renal osteodystrophy and circulating IGF-1 or -2 or IGFBP-2 and -3. This does not exclude that potential alterations of the local IGF system may play a role in the pathogenesis of uremic bone disease.

Severe hemorrhagic complications from infection with nephropathia epidemica strain of Hantavirus.

In the following we describe a case of severe hemorrhagic fever with renal syndrome (HFRS) caused by Puumala infection. The diagnosis was made by immunofluorescence technique and by solid phase enzyme immunoassay using recombinant nucleocapsid antigen of a Puumala serotype strain. Such a clinical course with severe bleeding complications is considered untypical for Puumala induced HFRS.

Long-term dialysis with low-calcium solution (1.0 mmol/L) in CAPD: effects on bone mineral metabolism. Collaborators of the Multicenter Study Group.

OBJECTIVE: Peritoneal dialysate solutions with conventionally high-calcium (Ca) concentrations (1.75 mmol/L) are now widely replaced by solutions with a lower, more physiological calcium content to prevent hypercalcemia in patients treated with oral calcium-containing phosphate binders and/or calcitriol. While there is still debate on how far the dialysate calcium should be lowered (1.25 mmol/L or less), little information is available concerning the effects of a long-term treatment with low-calcium solutions on secondary hyperparathyroidism and bone mineral metabolism in general. DESIGN: A prospective, randomized, controlled multicenter study to compare the effects of low-calcium (LCa, dialysate calcium 1.0 mmol/L) versus standard-calcium dialysate solution (SCa, dialysate calcium 1.75 mmol/L) on bone mineral metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients over 2 years of treatment. SETTING: Nephrology and dialysis units of primary and tertiary hospitals in Germany and Switzerland. PATIENTS: All CAPD patients in the participating centers between 18 and 80 years of age, stable on CAPD for at least 1 month, free of aluminium bone disease or prior parathyroidectomy were invited to enter the study. Sixty-four patients could be randomly allotted to LCa (n = 35) or SCa (n = 29) treatment in a 2-year protocol; 34 finished the study as planned. INTERVENTIONS: Calcium carbonate (CaCO3) was given as oral phosphate binder to maintain serum phosphate < 2.0 mmol/L. If hypercalcemia supervened, CaCO3 was exchanged stepwise for aluminium hydroxide (Al(OH)3), until normocalcemia was obtained. Patients received calcitriol (0.25 microgram/day per os) if parathyroid hormone (PTH) exceeded the upper limit of normal by a factor of 2 or more. MAIN OUTCOME MEASURES: We assessed total and ionized serum calcium, phosphate, serum aluminum, alkaline phosphatase, osteocalcin, PTH (intact molecule), and phosphate binder intake at regular intervals. Measurements of bone mineral density and hand skeleton x-rays were obtained at the start and after 6 months and 2 years, respectively. RESULTS: With LCa, mean total and ionized serum calcium levels were within the normal range (total Ca: 2.0-2.6 mmol/L; ionized Ca: 1.19-1.32 mmol/L), but throughout the treatment period were significantly lower than with SCa. The incidence of hypercalcemia (> 2.8 mmol/L) was three times higher in patients on SCa, despite the significantly higher amount of Al(OH)3 and less CaCO3 given in this group. In parallel, serum aluminum increased with SCa throughout the study, whereas it was slowly decreasing with LCa. Median PTH levels remained stable at about two times the upper limit of normal over the 2 years of study with LCa. However, 23% of the patients on LCa developed severe hyperparathyroidism, with PTH levels exceeding ten times the upper limit of normal compared to only 10.3% of the patients on SCa. With SCa, median PTH decreased towards near normal levels. Alkaline phosphatase and serum osteocalcin correlated positively with PTH levels. Bone mineral density was in the lower normal range in both groups and remained unchanged at the end of the study. Skeletal x-ray films showed only minor alterations in very few patients in both groups with no correlation to serum PTH or treatment modality. CONCLUSION: In CAPD patients low-calcium dialysate solutions can be used successfully over prolonged periods of time with stable control of serum calcium. The risk of hypercalcemia resulting from calcium-containing phosphate binders and the need to use aluminum-containing phosphate binders is markedly diminished. However, there is a certain risk that severe secondary hyperparathyroidism with long-term LCa therapy will develop, even if normocalcemia is maintained. Thus, LCa dialysis requires close and continuous monitoring of PTH and bone metabolism.

Transperitoneal calcium mass transfer using dialysate with a low calcium concentration (1.0 mM).

Lower dialysate calcium concentrations were recently proposed to overcome the risk of hypercalcemia in continuous ambulatory peritoneal dialysis (CAPD) patients on calcium-containing phosphate binders and/or vitamin D metabolites using the standard dialysate calcium concentration (SCa) of 1.75 mM. To assess transperitoneal calcium mass transfer (CaMT) in CAPD patients using a dialysate with a low calcium concentration (LCa, 1.00 mM), 18 stable patients were randomly allocated to receive either LCa or SCa. CaMT was assessed over 4 hours using 2L dialysate bags with three different dialysate glucose concentrations (1.5%, 2.3%, 4.25%). Total serum calcium (tCa), ionized calcium (iCa), and the exact dialysate volume were measured before and after the 4-hour dwell. A sample of the drained dialysate was obtained to measure the dialysate calcium concentration. The tCa and iCa levels were not significantly different in both groups prior to and did not change throughout the test. CaMT (median/range) was -0.64 mmol/exchange (-0.35(-)-1.29 mmol/exchange) using LCa with 1.5% glucose compared to 0.23 mmol (-0.18-0.87 mmol) with SCa (p < 0.0001). CaMT was negatively correlated to iCa and ultrafiltration volume [4.25%: LCa-1.22 (-0.84(-)-1.9); SCa -0.43 (-1.35-0.13); p < 0.001]. In summary, LCa results in a loss of calcium into the dialysate even at low ultrafiltration volumes and serum iCa levels. This might facilitate the prevention and therapy of renal osteodystrophy with calcium-containing phosphate binders and calcitriol. However, patients using LCa must be carefully monitored for calcium homeostasis and bone turnover.

[Does the primary disease recur in kidney transplantation?]. / Rekurriert die Grundkrankheit im Nierentransplantat?

Improved graft survival is accompanied by complications which interfere with the long-term function of the allograft. Recurrence of the primary renal disease in the graft is well recognized and is found in 10 to 20% of all recipients; however, graft loss due to recurrent disease is reported in less than 5% of all cases. The most frequent cause of recurrence is glomerulonephritis: Membrano-proliferative GN type II, IgA nephritis and focal sclerosis are frequently observed. Among metabolic disorders linked to graft disease, diabetic nephropathy has to be mentioned first. Primary oxalosis is a rare disorder, but it is related to a very high risk of recurrent disease in the transplant. Combined kidney-liver transplantation seems to offer a valuable alternative for these patients. The high risk of recurrence of certain diseases, i.e. membrano-proliferative GN type II, focal-segmental glomerulosclerosis, primary oxalosis, should prevent living donation. In addition, there are some reports suggesting that living-related donation might increase the recurrence rate of hemolytic-uremic syndrome, membranous GN and Schönlein-Henoch purpura. Recurrent disease might not only affect the outcome of the transplant, but can provide insight into the nature and pathogenesis of the primary disease. Currently there are no conclusive reports indicating that chronic immunosuppression, especially cyclosporin-A treatment, reduces recurrence rates; however the clinical course might be ameliorated.

[Dialysis therapy--indications and technical bases]. / Dialysetherapie--Indikation und technische Grundlagen.

Technical improvement in both, hemo- and peritoneal dialysis, has made these methods extremely safe and efficient. With an increasing number of patients entering a dialysis program for end-stage renal disease, the number of long-term dialysis patients, who will not receive a transplant for various reasons, will also increase. Modern dialysis treatment must not only keep the patient alive but has to allow for as much individual and social rehabilitation as possible. Indication, timing and predialysis preparations must be in the nephrologist's hands. However, for most patients the family's physician has been a partner and adviser during many years of a chronic disease. Therefore, he should be familiar with principles and practice of modern dialysis treatment. It is the aim of this paper to outline some basic principles of the most common dialysis modalities used today and to consider their pros and cons with respect to the patient's individual situation.

[Dialysis and ultrafiltration therapy in patients with cardio-renal syndrome: recommendations of the working group "heart-kidney" of the German Cardiac Society and the German Society of Nephrology]. / Dialyse- und Ultrafiltrationsverfahren bei kardio-renalem Syndrom. Empfehlung der Arbeitsgemeinschaft "Herz--Niere" der Deutschen Gesellschaft für Kardiologie--Herz- und Kreislaufforschung e.V. und der Deutschen Gesellschaft für Nephrologie e.V.

Renal failure is common in patients with severe heart failure. This complex pathophysiological interaction has been classified as cardio-renal syndrome. In these patients hydropic decompensation is the main cause of hospitalization. In patients with refractory heart failure, characterized by diuretic resistance and congestion due to volume overload, ultrafiltration has to be considered. In acute decompensated heart failure with worsening of renal function, extracorporeal ultrafiltration is the preferred treatment modality. On the other hand, patients suffering from chronic decompensated heart failure, particularly patients with ascites, will profit from the treatment specific advantages of peritoneal ultrafiltration. Prerequisite for an optimized care of patients with cardio-renal syndrome is the close collaboration among intensive care doctors, cardiologists and nephrologists.

Prevention of renal osteodystrophy in peritoneal dialysis.

BACKGROUND: Renal osteodystrophy (ROD) is still one of the major long-term complications in end-stage renal disease leading to considerable morbidity. Despite some progress in understanding the pathogenesis of secondary hyperparathyroidism (sHPT) during recent years, prevention and treatment of ROD is still suboptimal, requiring surgical parathyroidectomy in 6 to 10% of all patients on dialysis after 10 years. In addition, the spectrum of bone lesions has changed, with non-aluminum-related adynamic bone disease (ABD) found in up to 43% of peritoneal dialysis (PD) patients. METHODS: Current recommendations concerning prevention of ROD in PD based on the literature and personal recent data were reviewed. The focus is on (i) the importance of early prophylactic intervention to prevent parathyroid gland hyperplasia, (ii) the pathogenesis of ABD, and (iii) the role of metabolic acidosis in ROD. RESULTS: There is ample evidence that sHPT starts early during the course of renal failure and results from both hypersecretion of PTH by parathyroid cells and glandular hyperplasia. As shown by experimental and clinical studies, established parathyroid cell hyperplasia is hardly reversible by pharmacological means, and therefore prevention of parathyroid cell proliferation needs to start early. Recent data from randomized trials document the efficacy and safety of low dose active vitamin D (0.125 to 0.25 microgram/day) and/or an oral calcium substitute to prevent progression of sHPT in patients with mild to moderate renal failure. Since little is known about the pathogenesis, natural course and clinical impact of ABD in PD, specific therapeutic concepts have not yet been generated. Diabetes and advanced age are established risk factors, whereas the role of calcium and vitamin D overtreatment or the type of dialysis (PD vs. HD) are still controversial. Currently no evidence for different functional behavior of the parathyroids in ABD and sHPT has been found. The role of circulating or local factors such as cytokines, growth factors or the presence of advanced glycation end-product (AGE)-modified matrix proteins for the pathogenesis of either type of ROD deserves further investigation. Avoiding oversuppression of parathyroid gland and the use of low calcium dialysate may help prevent ABD. There is growing evidence that a correction of metabolic acidosis will influence ROD by both direct effects on the bone and on parathyroid cell function. New dialysate composition for CAPD with a high HCO3 concentration will allow normalization of acid-based metabolism in PD patients. Their effects on ROD under long term conditions remain to be determined. CONCLUSION: Therapeutic efforts should aim to prevent the development of parathyroid gland hyperplasia and sHPT early during the course of renal failure, and should include the use of low dose vitamin D therapy and oral calcium substitution as well as correction of metabolic acidosis. Concerning ABD, more information is needed regarding the causes and consequences of this type of bone lesion to develop a more specific therapy.

Malignant fibrous histiocytoma and atypical fibroxanthoma in renal transplant recipients.

BACKGROUND: Allograft recipients are at increased risk for skin cancer. The incidence of cutaneous squamous cell carcinoma is 50-250 times higher than in the age-matched control population, and basal cell carcinoma is about 10 times more frequent. The incidence of Kaposi's sarcoma is increased 400 to 500 times over that in a control population of the same ethnic origin. However, the incidence of other types of cutaneous sarcoma in organ allograft recipients is largely unknown. CLINICAL OBSERVATION: Within a 2-year-period, we observed 2 patients with cutaneous malignant fibrous histiocytoma and 1 patient with atypical fibroxanthoma among a cohort of 642 renal transplant recipients. For comparison, the incidence for dermatofibrosarcoma protuberans which is the commonest type of cutaneous sarcoma, is 0.45/100,000 persons/year in the non-immunocompromised population. Our observation represents an incidence of 156/100,000/ year (95% confidence interval Cl 28-489/100,000/year) for cutaneous malignant fibrous histiocytoma and of 78/100,000/year (95% CI 4-368/ 100,000/year) for atypical fibroxanthoma. CONCLUSION: To our knowledge, this is the first report on an elevated incidence of cutaneous malignant fibrous histiocytoma and of atypical fibroxanthoma in renal transplant recipients. Future cohort studies on malignancies in organ allograft recipients should aim at defining this risk more exactly.