Lithium Therapy in Old Age: Recommendations from a Delphi Survey.

INTRODUCTION: While lithium (Li) has been well established for the treatment of bipolar disorder, geriatric patients require special attention when it comes to issues of drug safety. Declining renal function, amongst other medical conditions, and polypharmacy may pose increased risks. Only a few previous studies have addressed the management of Li in geriatric patients. METHODS: Twenty-four German medical experts on geriatric medicine and Li treatment participated in a Delphi survey, consisting of two rounds of questionnaires and a final formulation of treatment recommendations. Three major issues of Li therapy were outlined: initiation of treatment, monitoring of ongoing therapy, and withdrawal due to medical reasons. Final recommendations were consented to at a threshold of at least 80% expert agreement. RESULTS: Final consensus was achieved on 21 clinical recommendations. The approved recommendations covered aspects of necessary laboratory checks, concomitant medication, and target Li serum concentration in geriatric patients. Concerning the termination of Li therapy, an agreement was reached on the appropriate time span for tapering and on potential alternatives to Li. No consensus was achieved on whether concomitant dementia or frailty should be considered contraindications for Li treatment and the appropriate threshold of the estimated glomerular function rate for withdrawing Li. CONCLUSION: According to the view of German experts, Li may be used in geriatric patients, but it should be monitored carefully. However, the lack of consent in several specific treatment situations underlines the need for research on specific issues of Li therapy.

Contrast medium free selective adrenal vein sampling in the management of primary aldosteronism.

BACKGROUND: To analyze contrast free adrenal vein sampling (AVS) for differentiating unilateral from bilateral disease in patients diagnosed with hypertension due to primary aldosteronism (PA). METHODS: Consecutive patients with PA and subsequent contrast medium free AVS between April 2015 and March 2020 were retrospectively included. Cross-sectional imaging (CSI), AVS and clinical data were analyzed regarding diagnostic performance. In addition, patients with lateralisation receiving adrenalectomy were compared to a control group treated with mineralocorticoid antagonists. RESULTS: In total 186 patients with AVS were included. The success rate for bilateral catheterization was 88% (median effective dose 2.8 mSv). CSI had an accuracy of 60% (CI: 0.52-0.67) in the detection of lateralization compared to AVS. Patients with bilateral adrenal hyperplasia and those with aldosterone-producing adenoma did not differ in systolic blood pressure (sBP) (p = 0.63) or number of antihypertensive drugs (NAD) (p = 0.11). After adrenalectomy, 28 patients were cured (51%; sBP ≤130 mmHg, NAD = 0), 18 were improved (33%; decrease of sBP ≥20 mmHg and NAD), and 8 were unchanged (15%). Serum renin increased significantly after treatment (p < 0.01). CONCLUSION: Contrast medium free AVS is a reliable procedure in the diagnostic management of patients with PA with high technical success rate. The accordance between CSI and results from AVS was only moderate indicating the central role of AVS in the diagnostic work-up of patients with PA. Patients with predominant disease diagnosed with AVS had a high cure rate and/or significant improvement after adrenalectomy.

Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism.

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.

Association between socioeconomic position and cystatin C in the Heinz Nixdorf Recall Study.

Social inequalities in health and disease are well studied. Less information is available on inequalities in biomarker levels indicating subclinical stages of disease such as cystatin C, an early diagnostic marker of renal dysfunction and predictor for cardiovascular disease. We evaluated the relationship between cystatin C, socioeconomic position (SEP) and established cardiovascular risk factors in a population-based study. In 4475 men and women aged 45-75 years participating in the baseline examination of the Heinz Nixdorf Recall Study cystatin C was measured from serum samples with a nephelometric assay. SEP was assessed by education and household income. Linear regression models were used to analyse the association between SEP and cystatin C as well as the impact of cardiovascular risk factors (i.e., body mass index, blood pressure, blood glucose, diabetes mellitus, blood lipids, C-reactive protein, smoking) on this association. After adjustment for age and sex cystatin C decreased by 0.019 mg/l (95% confidence interval (CI) - 0.030 to - 0.008) per five years of education. While using a categorical education variable cystatin C presented 0.039 mg/l (95% CI 0.017-0.061) higher in men and women in the lowest educational category (≤ 10 years of education) compared to the highest category (≥ 18 years). Concerning income, cystatin C decreased by 0.014 mg/l (95% CI - 0.021 to - 0.006) per 1000 € after adjustment for age and sex. For men and women in the lowest income quartile cystatin C was 0.024 mg/l (95% CI 0.009-0.038) higher compared to the highest income quartile. After adjusting for established cardiovascular risk factors the observed associations were substantially diminished. Social inequalities seem to play a role in subclinical stages of renal dysfunction, which are also related to development of cardiovascular disease. Adjustment for traditional cardiovascular risk factors showed that these risk factors largely explain the association between SEP and cystatin C.

Liquid biopsies: donor-derived cell-free DNA for the detection of kidney allograft injury.

In kidney transplantation, the use of minimally invasive damage biomarkers that are more sensitive and specific than plasma creatinine will be crucial to enable early, actionable detection or exclusion of structural kidney damage due to acute or chronic rejection. Donor-derived cell-free DNA (dd-cfDNA), which can be quantified, for example, through next-generation sequencing, droplet digital PCR and quantitative PCR, is a candidate biomarker with great potential for enabling comprehensive monitoring of allograft injury. dd-cfDNA has a favourable overall diagnostic performance for the detection of rejection and its high negative predictive value might be especially useful for avoiding unnecessary biopsies. Elevated dd-cfDNA levels have been shown to be detectable before graft injury can be clinically identified using current diagnostic methods. Moreover, dd-cfDNA falls rapidly to baseline levels after successful treatment for rejection owing to its short half-life. dd-cfDNA can detect graft injury caused by immune activation owing to insufficient immunosuppression and might therefore also help guide immunosuppression dosing. The fractional abundance of dd-cfDNA can be affected by changes in the recipient cfDNA (for example, due to infection or physical exercise) but the use of absolute quantification of dd-cfDNA overcomes this limitation. Serial dd-cfDNA determinations might therefore facilitate cost-effective personalized clinical management of kidney transplant recipients to reduce premature graft loss.

Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. / Update: Selektive Nebennierenvenenblutentnahme (NNVBE) ­ Indikation, Technik und Stellenwert.

BACKGROUND: Primary aldosteronism (PA) is the most common detectable cause of secondary hypertension. The majority of patients have either an adrenal aldosterone-producing adenoma (APA) or bilateral adrenal hyperplasia (BAH) demanding different therapeutic approaches. Screening tests and imaging cannot reliably distinguish between a unilateral or bilateral PA. METHODS: This review article gives an overview concerning etiology, diagnostics, and therapeutic options of PA, and reviews the indication, the technique, and relevance of selective adrenal venous sampling (AVS) in the context of the current literature and the authors' experience. RESULTS: AVS can verify or exclude a unilaterally dominated secretion with a high success rate. Patients with PA and a unilateral APA can be treated curatively by adrenalectomy. CONCLUSIONS: AVS is an established diagnostic examination for differentiation of unilateral from bilateral adrenal disease in patients with PA. KEY POINTS: · Selective adrenal venous sampling (AVS) is a safe, reliable, and minimally invasive method to detect a unilateral or bilateral adrenal adrenal gland disease.. · Verification of lateralization by AVS has direct therapeutic relevance for patients with primary aldosteronism (PA).. · AVS can be performed with low radiation exposure, without contrast medium, and with a high success rate when performed by an experienced interventional radiologist.. CITATION FORMAT: · Loberg C, Antoch G, Stegbauer J et al. Update: Selective adrenal venous sampling (AVS) - Indication, technique, and significance. Fortschr Röntgenstr 2021; 193: 658 - 666.

[Renal cortical necrosis after application of tranexamic acid in peripartal hemorrhage]. / Renale Rindennekrose nach Gabe von Tranexamsäure bei geburtsassoziierter Blutung.

HISTORY: A 28-years old patient delivers a daughter by primary caesarian section (41. WOP) in breech presentation after a complication-free pregnancy except increased blood pressure readings at the morning of caesarian section. During the caesarian section a major bleeding of the atonic uterus with hemorrhagic shock appears. Haemostasis is achieved by mechanical tamponade, the application of red blood cell concentrates and the substitution of clotting factors, also tranexamic acid. Because of an anuric renal failure due to the shock hemodialysis is initiated. EXAMINATIONS/FINDINGS: Clinical examination and blood tests show the constellation of a thrombotic microangiopathy. There are no hints for a thrombotic thrombocytopenic purpura (TTP) or a hemolytic-uremic syndrome (HUS). In addition, a genetic testing gives no hints for an atypical HUS. After 4 weeks of dialysis duty a renal biopsy is performed. The renal biopsy shows a partly reversible tubular damage with an older ischemic cortical necrosis. DIAGNOSIS/THERAPY: In the further course the resumption of the diuresis can be observed. The dialysis treatment has to be continued because of an insufficient excretory renal function. Fortunately a living-donor kidney transplantation (mother) can be carry out successfully already one year after the hemorrhagic shock. CONCLUSION: The combination of peripartal bleeding with hemorrhagic shock, possibly aggravated by (pre-)eclampsia or HELLP-syndrome, and the application of tranexamic acid with its prothrombotic effect seems to be responsible for the major renal cortical necrosis.

Mas receptor deficiency augments angiotensin II-induced atherosclerosis and aortic aneurysm ruptures in hypercholesterolemic male mice.

OBJECTIVE: Previous studies demonstrated that deficiency of angiotensin-converting enzyme 2 (ACE2) augmented angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysm (AAA) formation in hypercholesterolemic mice. Effects of ACE2 deficiency could arise from increased concentrations of its substrate, AngII, or decreased concentrations of its product, angiotensin-(1-7) [Ang-(1-7)]. Infusion of Ang-(1-7), a Mas receptor (MasR) ligand, to hypercholesterolemic male mice reduced AngII-induced atherosclerosis, suggesting a protective role of the Ang-(1-7)/MasR axis. However, it is unclear whether endogenous Ang-(1-7) acts at MasR to influence AngII-induced vascular diseases. The purpose of this study was to define the role of MasR deficiency in AngII-induced atherosclerosis and AAA formation and severity in hypercholesterolemic male mice. METHODS: MasR+/+ and MasR-/- male mice on a low-density lipoprotein receptor-deficient (Ldlr-/-) or apolipoprotein E-deficient (Apoe-/-) background were infused with AngII at either 600 or 1000 ng/kg/min by osmotic minipump for 28 days. Atherosclerosis was quantified at study end point as percentage lesion surface area of the aortic arch in Ldlr-/- mice. Abdominal aortic internal diameters were quantified by ultrasound, and maximal external AAA diameters were quantified at study end point. Blood pressure was quantified by radiotelemetry and a tail cuff-based technique. Serum cholesterol concentrations and vascular tissue characterization were examined at study end point. RESULTS: MasR deficiency did not influence body weight, systolic blood pressure at baseline and during AngII infusion, or serum cholesterol concentrations in either Apoe-/- or Ldlr-/- mice. MasR deficiency increased AngII-induced atherosclerosis in aortic arches of Ldlr-/- mice (P < .05), associated with increased oxidative stress and apoptosis in aortic root sections (P < .05). MasR deficiency also augmented internal and external AAA diameters and increased aortic ruptures of both Ldlr-/- and Apoe-/- mice (P < .05). These effects were associated with increased elastin breaks and T-lymphocyte and macrophage accumulation into abdominal aortas of AngII-infused MasR-deficient mice (P < .05). CONCLUSIONS: These results demonstrate that MasR deficiency augmented AngII-induced atherosclerosis and AAA rupture through mechanisms involving increased oxidative stress, inflammation, and apoptosis, suggesting that MasR activation may provide therapeutic efficacy against vascular diseases.

Angiotensin-(1-7)-induced Mas receptor activation attenuates atherosclerosis through a nitric oxide-dependent mechanism in apolipoproteinE-KO mice.

Angiotensin (Ang)-(1-7) ameliorates vascular injury by increasing nitric oxide (NO) bioavailability. Evidence that Ang-(1-7) attenuates the development of atherosclerosis through a NO-dependent mechanism is still missing. Moreover, it has been postulated that Ang-(1-7) may mediate its effects by other mechanisms than Mas receptor activation. To investigate Ang-(1-7)-dependent Mas receptor function, we treated apoE-KO and apoE/Mas-KO mice chronically with Ang-(1-7) (82 µg/kg per hour) or saline for 6 weeks. Flow-mediated dilation (FMD), a measure for NO-dependent vasodilation and the most accepted prognostic marker for the development of atherosclerosis, was measured in vivo. Chronic Ang-(1-7) treatment improved FMD and attenuated the development of atherosclerosis in apolipoproteinE (apoE)-KO but not in apoE/Mas-KO mice. These effects were accompanied by increased aortic nitrite and cGMP levels. To test whether Ang-(1-7) modulates atherosclerosis through a NO-dependent mechanism, apoE-KO mice were treated with the NO synthase inhibitor L-NAME (20 mg/kg/day) in the presence or absence of Ang-(1-7). L-NAME treatment reduced aortic nitrite content and increased blood pressure and exaggerated atherosclerosis compared to untreated apoE-KO mice. In L-NAME-treated apoE-KO mice, chronic Ang-(1-7) treatment did not increase aortic nitrite content and consequently showed no effect on blood pressure and the development of atherosclerosis. The present study proves that Ang-(1-7) mediates its protective vascular effects through Mas receptor activation. Moreover, Ang-(1-7)-mediated NO generation is essential for improving vascular function and prevents atherosclerosis in apoE-KO mice.

Impact of monocyte-macrophage inhibition by ibandronate on graft function and survival after kidney transplantation: a single-centre follow-up study over 15 years.

BACKGROUND: The aim of this study was to evaluate the effect of ibandronate administration on long-term graft function and graft survival after successful renal transplantation. METHODS: Seventy-two renal transplant recipients (36 patients each in the treatment and control group) were included and followed over a 15-year period. Data on graft function and death-censored transplant outcome were recorded at 1, 5, 10, and 15 years. RESULTS: Death-censored Kaplan-Meier analysis showed significantly improved graft survival of the treatment group (p = 0.026), whereas Cox regression analysis showed that ibandronate was positively associated with improved transplant survival (p = 0.028, hazard ratio 0.24, 95% confidence interval 0.07-0.86). Although general linear modelling did not indicate that ibandronate had a significant effect on transplant function (calculated using the estimated glomerular filtration rate according to Chronic Kidney Disease Epidemiology Collaboration equation) over the entire 15-year period (p = 0.650), there was a tendency towards improved graft function 1-year post-transplantion (p = 0.056). CONCLUSIONS: Ibandronate treatment within the first year of transplantation resulted in a trend towards better graft function within the first few year post-transplant, and was associated with increased transplant survival at long-term follow-up.

Worsening of lipid metabolism after successful treatment of primary aldosteronism.

Primary aldosteronism (PA) describes the most frequent cause of secondary arterial hypertension. Recently, deterioration of lipid metabolism after adrenalectomy (ADX) for aldosterone-producing adenoma (APA) has been described. We analysed longitudinal changes in lipid profiles in a large prospective cohort of PA patients. Data of 215 consecutive PA patients with APA (n = 144) or bilateral idiopathic adrenal hyperplasia (IHA, n = 71) were extracted from the database of the German Conn's Registry. Patients were investigated before and 1 year after successful treatment by ADX or by mineralocorticoid receptor antagonists (MRA). Glomerular filtration rate (GFR), fasting plasma glucose and components of lipid metabolism including triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined at 8.00 after a 12-h fasting period. One year after initiation of treatment mean serum potassium levels and blood pressure normalized in the patients. HDL-C and TG developed inversely with decreasing HDL-C levels in patients with APA (p = .046) and IHA (p = .004) and increasing TG levels (APA p = .000; IHA p = .020). BMI remained unchanged and fasting plasma glucose improved in patients with APA (p = .004). Furthermore, there was a significant decrease of GFR in both subgroups at follow-up (p = .000). Changes in HDL-C and TG correlated with decrease in GFR in multivariate analysis (p = .024). Treatment of PA is associated with a deterioration of lipid parameters despite stable BMI and improved fasting plasma glucose and blood pressure. This effect can be explained by renal dysfunction following ADX or MRA therapy.

Long-term graft outcome after renal arterial reconstruction during living related kidney transplantation.

BACKGROUND/OBJECTIVES: The aim of this retrospective study was to evaluate the repair of vascular variations/pathologies in living donor kidney transplantations in a single centre over a 15-year period. METHODS: Between 01/1997 and 05/2012, 338 living donor renal transplantations were performed in the Department for Endovascular and Vascular Surgery, University of Düsseldorf, Germany. Twenty-four of them showed disorders, like multiple renal arteries (MRA), atherosclerotic stenosis or fibromuscular dysplasia (FMD) needing vascular repair before transplantation. RESULTS: Mean age of donors was 51 ± 11.2, in recipient's 44 ± 13.9 years. In seven transplantations, renal artery (RA) repair was performed because of MRA. Atherosclerotic stenosis of the RA was apparent in 12 cases needing a repair with disobliteration. FMD was the reason in five transplantations for vascular repair. Complications like renal vessel thrombosis, lymphocele, heamorrhage, distal urinary leakage and ureteral obstruction was not significantly associated with RA reconstruction. Comparison of renal function in kidneys with reconstructed RA compared with kidneys without vascular repair showed no significant difference in primary function and serum creatinine up to the first year after transplantation. Mean follow-up was 75.6 ± 48.1 months. The 5-year graft survival rate for kidneys with RA repair was 88.5 vs. 93.4 % without reconstruction. CONCLUSIONS: We could show that RA pathologies, suitable repaired, are not a contraindication for transplantation with acceptable 5-year-graft-survival rates.

Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case-control study.

OBJECTIVE: To evaluate the effect of different treatment strategies on enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome. DESIGN: Multicentre retrospective case-control study. SETTING: 23 hospitals in northern Germany. PARTICIPANTS: 298 adults with enterohaemorrhagic E coli induced haemolytic uraemic syndrome. MAIN OUTCOME MEASURES: Dialysis, seizures, mechanical ventilation, abdominal surgery owing to perforation of the bowel or bowel necrosis, and death. RESULTS: 160 of the 298 patients (54%) temporarily required dialysis, with only three needing treatment long term. 37 patients (12%) had seizures, 54 (18%) required mechanical ventilation, and 12 (4%) died. No clear benefit was found from use of plasmapheresis or plasmapheresis with glucocorticoids. 67 of the patients were treated with eculizumab, a monoclonal antibody directed against the complement cascade. No short term benefit was detected that could be attributed to this treatment. 52 patients in one centre that used a strategy of aggressive treatment with combined antibiotics had fewer seizures (2% v 15%, P = 0.03), fewer deaths (0% v 5%, p = 0.029), required no abdominal surgery, and excreted E coli for a shorter duration. CONCLUSIONS: Enterohaemorrhagic E coli induced haemolytic uraemic syndrome is a severe self limiting acute condition. Our findings question the benefit of eculizumab and of plasmapheresis with or without glucocorticoids. Patients with established haemolytic uraemic syndrome seemed to benefit from antibiotic treatment and this should be investigated in a controlled trial.

Renal hemodynamics and renal function after catheter-based renal sympathetic denervation in patients with resistant hypertension.

Increased renal resistive index and urinary albumin excretion are markers of hypertensive end-organ damage and renal vasoconstriction involving increased sympathetic activity. Catheter-based sympathetic renal denervation (RD) offers a new approach to reduce renal sympathetic activity and blood pressure in resistant hypertension. The influence of RD on renal hemodynamics, renal function, and urinary albumin excretion has not been studied. One hundred consecutive patients with resistant hypertension were included in the study; 88 underwent interventional RD and 12 served as controls. Systolic, diastolic, and pulse pressure, as well renal resistive index in interlobar arteries, renal function, and urinary albumin excretion, were measured before and at 3 and 6 months of follow-up. RD reduced systolic, diastolic, and pulse pressure at 3 and 6 months by 22.7/26.6 mm Hg, 7.7/9.7 mm Hg, and 15.1/17.5 mm Hg (P for all <0.001), respectively, without significant changes in the control group. SBP reduction after 6 months correlated with SBP baseline values (r=-0.46; P<0.001). There were no renal artery stenoses, dissections, or aneurysms during 6 months of follow-up. Renal resistive index decreased from 0.691±0.01 at baseline to 0.674±0.01 and 0.670±0.01 (P=0.037/0.017) at 3- and 6-month follow-up. Mean cystatin C glomerular filtration rate and urinary albumin excretion remained unchanged after RD; however, the number of patients with microalbuminuria or macroalbuminuria decreased. RD reduced blood pressure, renal resistive index, and incidence of albuminuria without adversely affecting glomerular filtration rate or renal artery structure within 6 months and appears to be a safe and effective therapeutic approach to lower blood pressure in patients with resistant hypertension.

Comparable outcome of acute unplanned peritoneal dialysis and haemodialysis.

BACKGROUND: The impact of dialysis modality on outcome, especially on infection early in the course of dialysis, in unplanned acute dialysis initiation has not been well evaluated. The aim of the study was to compare the rates and causes of mortality and morbidity in incident dialysis patients started unplanned acute peritoneal dialysis (PD) or haemodialysis (HD). PATIENTS AND METHODS: In this observational cohort study, incident dialysis patients with initiation of unplanned and acute PD (n = 66) or HD (n = 57) at a single centre from March 2005 to June 2010 were included and followed up for 6 months (0-183 days, mean follow-up time 4.72 months). For PD, surgically placed Tenckhoff catheters were used. All HD patients were dialysed with a central venous catheter (non-tunnelled or tunnelled). There were no significant differences in terms of gender, age and prevalence of diabetes mellitus in either group. The prevalence of heart failure [New York Heart Association (NYHA) Stage III-IV] was significantly higher in the PD group (73 versus 46% in HD group, P < 0.01). The population was stratified to PD and HD comparing mortality, infection, bacteraemia and hospitalization. RESULTS: Of the 123 patients who commenced acute and unplanned dialysis, n = 44 (35.8%) died during the follow-up period of 0-183 days. There were no significant difference in half-year mortality in n = 20 PD patients (30.3%) versus n = 24 HD patients (42.1%) (P = 0.19). The cardiovascular mortality in PD and HD patients were 9.1 and 10.5%, respectively (P = 1.00). Overall mortality due to infection was higher in the HD (17.5%) versus in the PD group (9.1%), however, not significant (P = 0.19). HD patients had significantly higher probability of bacteraemia in the first 183 days compared to PD patients (21.1 versus 3.0%, P < 0.01). Group comparison by Poisson regression analyses showed that the relative risk of bacteraemia in the PD group versus HD group was 0.16 (95% confidence interval, 0.05-0.57, P = 0.005). The significant difference was not affected by the confounder's patient age at time of dialysis, male sex, heart failure (NYHA III-IV), diabetes, malignancy and peripheral arterial occlusive disease Stage IV. There were high proportions of hospitalization after the initiation of dialysis in both groups (PD 75.0% and HD 67.3%, P = 0.40). Univariate and multiple regression analyses revealed only age at initiation of dialysis to be significantly associated with overall mortality (P < 0.05). CONCLUSIONS: Dialysis modality (PD versus HD) in an acute unplanned dialysis setting showed, in our population, no significant influence on survival. HD patients had a significantly higher risk of bacteraemia, perhaps due to central venous dialysis catheter. PD seems to be a safe and efficient, at least comparable, alternative to HD in acute unplanned dialysis settings.

Cystatin C - a fast and reliable biomarker for glomerular filtration rate in head and neck cancer patients.

PURPOSE: Determination of renal function is a prerequisite for planning therapy in cancer patients. Limitations of creatinine as marker for the glomerular filtration rate (GFR) led to the proposal of cystatin C as a more accurate biomarker especially in mild renal insufficiency or in patients with low muscle mass. We compared the accuracy of cystatin C- and creatinine-based equations to estimate GFR in head and neck cancer (HNC) patients receiving platinum-based radiochemotherapy. PATIENTS AND METHODS: The study population consisted of 52 HNC patients (GFR range, 37-105 mL/min/1.73 m(2) complemented by 17 patients with known renal insufficiency (GFR range, 10-60 mL/min/1.73 m(2)). Intraclass correlation coefficients were calculated between the reference method (51)Cr-EDTA clearance and estimated GFR by creatinine clearance and equations based on creatinine (Cockroft-Gault, modification of diet in renal disease (MDRD), Wright) or cystatin C (Larsson, Dade-Behring, Hoek). In addition, sensitivity and specificity to discriminate GFR > 60 mL/min/1.73 m(2) were evaluated by receiver operating characteristic curve (ROC). RESULTS: The highest correlation coefficients were found for the cystatin C-based estimates in comparison with creatinine-based estimates or creatinine clearance, even though Bland-Altman plots revealed GFR overestimation for all equations tested. The cystatin C-based Hoek formula exhibited the highest overall precision and accuracy. GFR of < 60 mL/min/1.73 m(2) was assumed as a cut-off for chemotherapy. ROC analyses revealed the highest AUC to predict a GFR > 60 mL/min/1.73 m(2) for the creatinine-based Wright formula, closely followed by the MDRD formula and cystatin C-based equations of Larsson, Dade-Behring, and Hoek. CONCLUSION: Cystatin C-based GFR estimates showed the overall strongest correlation to the reference method. Thus, we recommend cystatin C for GFR estimation in HNC patients as an alternative method to the estimated creatinine clearance in clinical practice.

Regulation of renal sympathetic neurotransmission by renal α(2A)-adrenoceptors is impaired in chronic renal failure.

BACKGROUND AND PURPOSE: The mechanisms underlying increased renal noradrenaline in renal failure are still unclear. In this study, the role of α(2A)-adrenoceptors in controlling sympathetic neurotransmission in chronic renal failure was evaluated in a subtotal nephrectomy model. Also, the influence of this receptor subtype on angiotensin II (Ang II)-mediated noradrenaline release was evaluated. EXPERIMENTAL APPROACH: α(2A)-adrenoceptor-knockout (KO) and wild-type (WT) mice underwent subtotal (5/6) nephrectomy (SNx) or SHAM-operation (SHAM). Kidneys of WT and KO mice were isolated and perfused. Renal nerves were stimulated with platinum electrodes and noradrenaline release was measured by HPLC. KEY RESULTS: Noradrenaline release induced by renal nerve stimulation (RNS) was significantly increased in WT mice after SNx. RNS-induced noradrenaline release was significantly higher in SHAM-KO compared with SHAM-WT, but no further increase in noradrenaline release could be observed in SNx-KO. α-adrenoceptor antagonists increased RNS-induced noradrenaline release in SHAM-WT but not in SHAM-KO. After SNx, the effect of α2-adrenoceptor blockade on renal noradrenaline release was attenuated in WT mice. The mRNA expression of α(2A)-adrenoceptors was not altered, but the inhibitory effect of α2-adrenoceptor agonists on cAMP formation was abolished after SNx. Ang II facilitated RNS-induced noradrenaline release in SHAM-WT but not in SHAM-KO and SNx-WT. CONCLUSION AND IMPLICATIONS: In our model of renal failure autoregulation of renal sympathetic neurotransmission was impaired. Presynaptic inhibition of noradrenaline release was diminished and the facilitatory effect of presynaptic angiotensin AT1 receptors on noradrenaline release was markedly decreased in renal failure and depended on functioning α(2A)-adrenoceptors.

Balance of profibrotic and antifibrotic [corrected] signaling in nephrogenic systemic fibrosis skin lesions.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) is an uncommon fibrotic disorder occurring after administration of linear gadolinium contrast agents in patients with severely decreased kidney function. The underlying pathogenetic mechanism of fibrosis remains to be elucidated. Transforming growth factor beta (TGF-beta), a key player in the pathogenesis of fibrotic disorders, has been found to be overexpressed in NSF skin lesions. The aim of this study is to analyze the TGF-beta-SMAD-connective tissue growth factor (CTGF) axis in NSF skin lesions compared with skin specimens from patients with systemic sclerosis, hemodialysis patients without NSF, and healthy controls. Additionally, expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and antifibrotic tumor necrosis factor alpha (TNF-alpha) were examined. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: Full-thickness skin biopsy specimens from fibrotic lesions or healthy skin were obtained from 10 patients with NSF, 16 patients with systemic sclerosis, 8 non-NSF hemodialysis patients, and 17 healthy participants. PREDICTOR: Patient diagnosis of NSF, systemic sclerosis, non-NSF hemodialysis patients, and healthy participants, as defined using skin biopsy. OUTCOME & MEASUREMENTS: Dermal messenger RNA and protein expression of profibrotic TGF-beta, SMAD2, SMAD3, SMAD4, SMAD7, CTGF, TIMP-1, antifibrotic SMAD7, and TNF-alpha were analyzed using real-time reverse transcription-polymerase chain reaction and immunohistologic examination on formalin-embedded tissue. RESULTS: Dermal expression of nearly all parameters differed in hemodialysis patients compared with healthy controls. In comparison to hemodialysis patients and healthy participants, we found increased messenger RNA levels for TGF-beta, the profibrotic receptor-activated SMAD2 and SMAD3, CTGF, and TIMP-1 in NSF and systemic sclerosis lesions. Few differences between NSF and non-NSF hemodialysis patients were observed for common SMAD4, inhibitory SMAD7, and TNF-alpha. LIMITATIONS: Small patient cohort. CONCLUSION: Our results suggest a profibrotic imbalance in the TGF-beta-SMAD-CTGF axis in NSF skin lesions. Significantly increased dermal expression of TGF-beta and TIMP-1 in non-NSF hemodialysis patients in comparison to healthy participants emphasizes the need for a hemodialysis control group for future investigations and suggests a pre-existing profibrotic situation in the skin of hemodialysis patients.

[The role of aldosterone in hypertension]. / Aldosteron und Hypertonie.

Hyperaldosteronism is associated with elevated cardiovascular risk. Using mineralocorticoid receptor antagonists a significant reduction in mortality was archived in patients with heart failure. In addition, in refractory hypertension and in patients with metabolic syndrome aldosterone seems to play an important role. Therapy with mineralocorticoidreceptor (MR) antagonists is feasible when aldosterone levels are elevated, in particular in patients with aldosterone-escape. Of particular interest is primary aldosteronism (PA). PA is one of the major causes of secondary hypertension. Since most patients with PA present with normokalemia screening has to be performed using the aldosterone renin ratio, in particular patients with refractory hypertension, young hypertensive patients and patients with incidentaloma. One has to point out that drugs that interfere with the aldosterone-renin-aldosterone-system need to be discontinued or changed. After successful screening, confirmatory testing (e.g. i.v. salt suppression test) has to follow. In order to differentiate between unilateral and bilateral disease computed tomography and adrenal vein sampling are performed. While unilateral adenomas can be cured surgically, bilateral adrenal hyperplasia is treated with MR-antagonists. In case of positive family history for PA one should consider familiar hyperaldosteronism (FH). Three forms are currently defined--FH type I, type II and type III. A hybrid gene consisting of CYP11B1 and CYP11B2 that produces aldosterone in an ACTH dependant manner can be found in FH type I. Diagnosis is verified by long range PCR. No underlying monogenetic cause for FH II and FH II could be detected so far. Through mechanisms way more than water and salt regulation, hyperaldosteronism can negatively influence cardiovascular mortality and morbidity and should therefore play an important part in diagnosis and therapy of arterial hypertension.

Nephrogenic systemic fibrosis--a rapidly progressive disabling disease with limited therapeutic options.

BACKGROUND: Nephrogenic systemic fibrosis (NSF) affects some patients on dialysis after gadolinium contrast agent-enhanced magnetic resonance imaging. It is characterized by progressive skin fibrosis of the extremities, sometimes including the trunk and internal organs. METHODS: The clinical course of 10 patients with biopsy-proven NSF was analyzed retrospectively with regard to gadolinium exposition, disease onset, and progression of NSF with special emphasis on physical mobility and impact of different therapeutic approaches. RESULTS: Despite physiotherapy and different additional therapeutic approaches (eg, immunosuppression, ultraviolet A-1 phototherapy, or extracorporal photopheresis) all patients developed progressive skin fibrosis of the lower extremities, sometimes including the trunk and arms. Kidney transplantation led to a slow improvement of skin lesions in one patient. Nine patients developed progressive joint contractures, and 8 patients became wheelchair bound within 12 months after disease onset and became dependent on the support of family members or a nursing service. LIMITATIONS: Retrospective analysis in a relatively small number of patients is a limitation. CONCLUSION: NSF appears to be a rapidly progressive disabling disease with limited therapeutic options.