Feasibility of renal perfusion quantification by Fourier decomposition MRI.

PURPOSE: To evaluate the feasibility of perfusion measurements in the human kidney by Fourier decomposition MRI (FD-MRI). METHODS: Renal perfusion measurements by FD-MRI and arterial spin labeling (ASL) were performed using a 1.5 T whole-body MR-scanner (Magnetom Avanto, Siemens Healthineers AG, Germany) in 15 healthy volunteers (mean age 33.0 ± 13.6 years). Five healthy volunteers were measured twice to evaluate the reproducibility. Besides, five patients with renal artery stenosis (RAS) (mean age 58.4 ± 16.2 years) were included in the study to evaluate potential clinical use of the FD-MRI for evaluating renal perfusion. For renal FD-MRI, coronal 2D-TrueFisp sequence (1 section; section thickness: 10 mm; FOV: 400 × 400 mm 2; TR/TE: 2.06/0.89 ms; 250 images; 0,36 s/image), for renal ASL, coronal FAIR-TrueFisp sequence (1 section; section thickness: 10 mm; FOV: 400 × 400 mm2; TR/TE 4.0/2.0 ms, TI 1200 ms, 30 averages; 8,32 s/average) were acquired without any triggering. Perfusion parameter maps of the kidneys were calculated for both methods. After manual segmentation, ROI-based analysis (whole kidney, cortex and medulla, respectively) was performed and the results were subsequently compared using the Student t-test. RESULTS: The acquisition times were 1.30 min and 4.16 min, for renal FD-MRI and ASL, respectively. No significant difference in global renal perfusion (RBF) between both methods was detected (mean RBF in the right kidney: 308.4 ± 31.5 mL/100 mL/min for FD-MRI; 315.2 ± 41.1 for ASL; in the left kidney: 315.6 ± 32.8 mL/100 mL/min for FD-MRI; 310.2 ± 39.1 mL/100 mL/min for ASL, respectively). The results indicated good reproducibility of both considered methods. However, cortico-medullar differentiation was not possible by FD-MRI, probably due to lower SNR compared to ASL. Significant difference in the side-separated RBF were measured by FD-MRI as well as by ASL (p < 0.05) in patients with RAS. CONCLUSIONS: FD-MRI is a novel, rapid approach for contrast-free perfusion quantification in the human kidney. Main advantage of this new method compared to ASL perfusion is the significant shorter acquisition time and lower dependency on patient's compliance. However, lower SNR of FD-MRI needs further improvement to make FD-MRI a competitive alternative to ASL.

Impact of low-dose steroids on HbA1c levels and development of pre-diabetes and NODAT in non-diabetic renal transplant recipients on long-term follow-up.

BACKGROUND: This study aimed to evaluate the impact of 5 mg of prednisolone/day on HbA1c levels and its association with the development of pre-diabetes and new-onset diabetes mellitus (NODAT) in non-diabetic first renal transplant recipients on long-term follow-up. METHODS: Four hundred patients were analysed on an average of 4.1 ± 3.0 years after successful transplantation: 96 (24%) were steroid-free and 304 (76%) treated with 5 mg of prednisolone/day combined with cyclosporine A (CsA) or tacrolimus (Tac) as part of their immunosuppressive protocol. Pre-diabetes and NODAT were defined based on the HbA1c levels according to the current ADA guidelines. The Mann-Whitney U test and the Chi-square test were used to determine intergroup differences. Multivariate logistic regression analyses (adjusted for steroid-free versus 5 mg of prednisolone per day, body mass index (BMI), number of HLA mismatches, eGFR according to the CKD-EPI formula, sex, negative vs. positive PRA titre, CMV and HCV positivity of the recipient, CsA vs. Tac immunosuppressive medication, dialysis vintage (years), age at the last follow-up and time from transplantation to the last follow-up) were performed to identify an independent effect of low-dose steroids on the evolution of pre-diabetes and NODAT. RESULTS: A small but statistically significant difference in HbA1c levels was observed between the control and the steroid groups (5.56 ± 0.54 vs. 5.67 ± 0.0.45%, p = 0.045). The incidence rates of pre-diabetes and NODAT per 100 patients per year were 9.3 and 3.0, respectively. Regression analysis showed that low-dose steroids (p = 0.026, risk ratio (RR) 1.789, 95%; confidence interval (CI) 1.007-3.040) and age (p = 0.000, RR 1.037/year, 95% CI 1.018-1.057) were associated with pre-diabetes, whereas BMI (p = 0.000, RR 1.190, 95% CI 1.084-1.307), age (p = 0.000, RR 1.087/year, 95% CI 1.047-1.129) and Tac use (p = 0.010, RR 3.300, 95% CI 1.328-8.196) were associated with NODAT. CONCLUSION: Using 5 mg of prednisolone/day was associated with increased HbA1c levels and an increased risk in developing pre-diabetes, but not NODAT, whereas BMI, age and the use of tacrolimus were associated with an increased risk in developing NODAT.

Chronic p38 mitogen-activated protein kinase inhibition improves vascular function and remodeling in angiotensin II-dependent hypertension.

INTRODUCTION: An excess of angiotensin II (Ang II) causes hypertension and vascular injury. Activation of mitogen-activated protein kinase p38 (p38-MAPK) plays a substantial role in Ang II-dependent organ damage. Recently, we showed that p38-MAPK activation regulates the pressor response to Ang II. This study evaluates the effect of chronic p38-MAPK inhibition in Ang II-dependent hypertension. MATERIALS AND METHODS: C57Bl/6J mice were infused with Ang II for 14 days and either treated with the p38-MAPK inhibitor BIRB796 (50 mg/kg/day) or the vehicle as the control. We assessed vascular function in the aorta and isolated perfused kidneys. RESULTS: Chronic p38-MAPK inhibition did not alter blood pressure at the baseline, but attenuated Ang II-induced hypertension significantly (baseline: 122 ± 2 versus 119 ± 4 mmHg; Ang II: 173 ± 3 versus 155 ± 3 mmHg; p < 0.001). In addition, BIRB796 treatment improved vascular remodeling by reducing the aortic media-to-lumen ratio and decreasing the expression of the membrane metalloproteinases (MMP) MMP-1 and MMP-9. Moreover, renal vascular dysfunction induced by chronic Ang II infusion was significantly ameliorated in the BIRP796-treated mice. Acute p38-MAPK inhibition also improved vascular function in the aorta and kidneys of Ang II-treated mice, highlighting the important role of p38-MAPK activation in the pathogenesis of vascular dysfunction. CONCLUSIONS: Our findings indicated there is an important role for p38-MAPK in regulating blood pressure and vascular injury, and highlighted its potential as a pharmaceutical target.

Prevalence of Malignancies in Patients With Primary Aldosteronism.

CONTEXT: Primary aldosteronism (PA) is the most common cause of secondary hypertension. Aldosterone excess can cause DNA damage in vitro and in vivo. Single case reports have indicated a coincidence of PA with renal cell carcinoma and other tumors. However, the prevalence of benign and malignant neoplasms in patients with PA has not yet been studied. PATIENTS AND DESIGN: In the multicenter MEPHISTO study, the prevalence of benign and malignant tumors was investigated in 335 patients with confirmed PA. Matched hypertensive subjects from the population-based Study of Health in Pomerania cohort served as controls. RESULTS: Of the 335 PA patients, 119 (35.5%) had been diagnosed with a tumor at any time, and 30 had two or more neoplasms. Lifetime malignancy occurrence was reported in 9.6% of PA patients compared to 6.0% of hypertensive controls (P = .08). PA patients with a history of malignancy had higher baseline aldosterone levels at diagnosis of PA (P = .009), and a strong association between aldosterone levels and the prevalence of malignancies was observed (P = .03). In total, 157 neoplasms were identified in the PA patients; they were benign in 61% and malignant in 25% of the cases (14% of unknown dignity). Renal cell carcinoma was diagnosed in five patients (13% of all malignancies) and was not reported in controls CONCLUSION: Compared to hypertensive controls, the prevalence of malignancies was positively correlated with aldosterone levels, tended to be higher in PA patients, but did not differ significantly.

Mass Spectrometry-Based Adrenal and Peripheral Venous Steroid Profiling for Subtyping Primary Aldosteronism.

BACKGROUND: Differentiating patients with primary aldosteronism caused by aldosterone-producing adenomas (APAs) from those with bilateral adrenal hyperplasia (BAH), which is essential for choice of therapeutic intervention, relies on adrenal venous sampling (AVS)-based measurements of aldosterone and cortisol. We assessed the utility of LC-MS/MS-based steroid profiling to stratify patients with primary aldosteronism. METHODS: Fifteen adrenal steroids were measured by LC-MS/MS in peripheral and adrenal venous plasma from AVS studies for 216 patients with primary aldosteronism at 3 tertiary referral centers. Ninety patients were diagnosed with BAH and 126 with APAs on the basis of immunoassay-derived adrenal venous aldosterone lateralization ratios. RESULTS: Among 119 patients confirmed to have APAs at follow-up, LC-MS/MS-derived lateralization ratios of aldosterone normalized to cortisol, dehydroepiandrosterone, and androstenedione were all higher (P < 0.0001) than immunoassay-derived ratios. The hybrid steroids, 18-oxocortisol and 18-hydroxycortisol, also showed lateralized secretion in 76% and 35% of patients with APAs. Adrenal venous concentrations of glucocorticoids and androgens were bilaterally higher in patients with BAH than in those with APAs. Consequently, peripheral plasma concentrations of 18-oxocortisol were 8.5-fold higher, whereas concentrations of cortisol, corticosterone, and dehydroepiandrosterone were lower in patients with APAs than in those with BAH. Correct classification of 80% of cases of APAs vs BAH was thereby possible by use of a combination of steroids in peripheral plasma. CONCLUSIONS: LC-MS/MS-based steroid profiling during AVS achieves higher aldosterone lateralization ratios in patients with APAs than immunoassay. LC-MS/MS also enables multiple measures for discriminating unilateral from bilateral aldosterone excess, with potential use of peripheral plasma for subtype classification.

Ibandronate in stable renal transplant recipients with low bone mineral density on long-term follow-up.

BACKGROUND: Bone mineral density (BMD) has been reported to increase without specific treatment in long-term renal transplant recipients. The aim of this study was to evaluate the effect of ibandronate on BMD and kidney function in long-term renal transplant recipients as compared to a control group. Furthermore, we searched for a gender-specific treatment effect of ibandronate on BMD. METHODS: In a retrospective, matched case-control study 60 stable renal transplant recipients were included on long-term follow-up. The patient cohort was divided into two groups. The control group (n = 30) comprised patients with close-to-normal bone mineral density who did not receive ibandronate treatment and the treatment group (n = 30) comprised patients with reduced bone mineral density who received ibandronate treatment. The groups were matched for sex, age at the time of renal transplantation, use of steroids, renal transplant function and time lag between the dual-energy X-ray absorptiometry (DEXA) measurements and renal transplantation. Patients of the treatment group were treated with 12.0 ± 6.7 g ibandronate. Treatment cycles lasted 19.3 ± 11.0 months. The first bone mineral density testing was performed 55.3 ± 60.2 months after renal transplantation followed by a second measurement 26.8 ± 12.1 months later. RESULTS: Both groups did not differ in absolute (g/cm(2)) or relative (%) changes in BMD at the lumbar spine (0.033 ± 0.079 vs. 0.055 ± 0.066 g/cm(2), p = 0.217 and 3.6 ± 7.8 vs. 6.4 ± 8.1 %, p = 0.124) or femoral neck (0.013 ± 0.106 vs. 0.025 ± 0.077 g/cm(2), p = 0.647 and 3.2 ± 13.6 vs. 5.0 ± 13.1 %, p = 0.544) over the study period. There was no correlation of ibandronate dosages with changes in BMD (LS: r = -0.089; p = 0.639 and FN: r =+0.288; p = 0.445). We could neither determine a negative effect of ibandronate on renal transplant function over the study period, estimated via the CKD-EPI formula (-2.9 ± 7.6 vs. -2.7 ± 10.6 mL/min/1.73 m(2), p = 0.900) nor a gender-specific action of ibandronate on bone mass changes. CONCLUSIONS: Ibandronate treatment was safe with respect to renal transplant function but did not result in a significant additive improvement in bone mineral density as compared to the untreated control group. A gender-specific action of ibandronate on BMD at the LS or FN could not be determined either.

[Renal replacement therapy in the intensive care unit]. / Nierenersatztherapie auf der Intensivstation.

BACKGROUND: Acute kidney injury is still one of the most common serious complications in critical ill patients and is associated with high mortality. Even small changes in renal function significantly influence survival and long-term prognosis. MATERIAL AND METHODS: Selective literature research and analysis of intensive care population with renal failure. CONCLUSION: Prophylactic measures as well as early diagnosis and therapy must be the goal of a modern intensive care treatment. Various treatment modalities for renal replacement therapy allow individualized treatment of each patient. The review summarizes the main aspects on prophylaxis and early diagnosis of acute kidney injury as well as the different treatment modalities for an individualized renal replacement therapy.

[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.

[When is the right time point to start dialysis?]. / Wann ist der richtige Zeitpunkt des Dialysebeginns?

The transition from CKD 5 to dialysis treatment (CKD 5 D) is characterized by a high mortality risk for patients with chronic kidney disease (CKD). Therefore, the right time to start dialysis is of special interest. While there was a trend towards an earlier initiation of dialysis many years ago, new studies could not demonstrate a benefit on survivals for patients who start dialysis in a higher glomerular filtration rate (GFR). Delaying the start of dialysis to a lower GFR is possible in CKD patients with stable conditions when close nephrological supervision is provided. In patients with cardiorenal syndrom and acute on chronic renal failure, an earlier start of dialysis might be necessary as well as the re-evaluation after re-compensation. In elderly patients the possibilities and risks of a conservative treatment without dialysis should be discussed. Consequently, current guidelines define the optimal time to start dialysis on the basis of the individual risk of the patients, clinical symptoms and underlying disease and not only on the GFR alone.

Assay characteristics influence the aldosterone to renin ratio as a screening tool for primary aldosteronism: results of the German Conn's registry.

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn's Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p<0.0001), renin concentration (p<0.001), and renin activity (p=0.009) for the different assays. The differences between the absolute concentrations measured by the different assays also had significant impact upon the resulting mean ratios. If published cutoff values are applied, the use of different commercial assays to determine the ARR in clinical routine results in major differences in positive screening rates. This heterogeneity affects sensitivity and specificity of screening for PA. Our data emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.

[Hypertensive emergency with clinical signs of a thrombotic microangiopathy]. / Hypertensiver Notfall mit den klinischen Symptomen einer thrombotischen Mikroangiopathie.

HISTORY AND ADMISSION FINDINGS: A 38-year-old woman presented with strong headache, abdominal and chest pain. Blood pressure was 240/115 mmHg. In the emergency room lab troponin T was elevated. Further tests showed signs of hemolysis and thrombopenia. In addition kidney failure was present. INVESTIGATIONS: The ECG showed tachycardia, but no other changes. Echocardiography revealed hypertrophy of the left ventricle. In the eye exam hypertensive retinopathy was demonstrated. Kidney biopsy showed signs compatible with malignant hypertension. TREATMENT AND COURSE: Due to chest pain and elevation of troponin T acute coronary syndrome was diagnosed. In combination with thrombopenia and hemolysis a thrombotic microangiopathy was suspected. Because of the hypertensive emergency malignant hypertension became a possible differential diagnosis. Unfortunately antiplatelet treatment precluded kidney biopsy right at the beginning. Thus, plasmapheresis was initiated together with antihypertensive treatment. Kidney biopsy was done after plasma exchange and confirmed the diagnosis of malignant hypertension. CONCLUSION: Diagnosis of malignant hypertension can be difficult because symptoms of thrombotic microangiopathy are frequently present. In many cases only the combination of history, exams of endorgan damage and clinical course is needed to confirm the diagnosis. Prompt and sustained lowering of the blood pressure is pivotal. Even after successful treatment patients keep an elevated cardiovascular risk and need a close follow up.

[Treatment resistant hypertension. Value of a new treatment concept]. / Therapierefraktäre Hypertonie. Stellenwert neuer Therapiekonzepte.

Sympathetic overexpression can be found in a majority of hypertensive patients. Resistant arterial hypertension requires a targeted diagnostic procedure in order to exclude secondary causes of hypertension which can be treated specifically with established therapies. If secondary reasons are not identified, the antihypertensive medication is already optimal and lifestyle changes have been realized, but still the goal of antihypertensive therapy cannot be achieved, alternative invasive therapy strategies such as renal sympathetic denervation and baroreflex activation have been developed to achieve blood pressure control. These therapies are restricted to specialized centers which treat well-defined patients with therapy-resistant hypertension. Little long-term data concerning safety and efficacy are available for the two strategies. However, they should preferably be used as an ultima-ratio and add-on pathway to conservative procedures when established medication fails to achieve blood pressure control. To date, the effectiveness of the interventional antihypertensive therapies has only been shown on patients with systolic blood pressure over 160 mmHg and a mean oral medication of five drugs.

[Renal insufficiency and cardiovascular diseases]. / Niereninsuffizienz und kardiovaskuläre Erkrankungen.

Chronic kidney disease (CKD) is a strong cardiovascular risk factor. Microalbuminuria is an early indicator of renal and cardiac damage. Optimal blood pressure therapy and reduction of proteinuria are important measures in order to reduce increased cardiovascular morbidity and mortality in this cohort. Secondary prevention by optimal medical as well as interventional therapy is employed in an inadequate number of CKD patients. In addition, CKD patients should be screened for sleep-related disorders and, if required, adequate therapy should be provided in order to improve cardiovascular outcome. Prospective data in advanced CKD patients concerning new therapeutical approaches such as oral factor Xa- or thrombin-inhibitor therapy are lacking. Optimal treatment of atrial fibrillation in dialysis patients with vitamin K antagonists is also unclear. Prospective studies of transcatheter aortic valve implantation for severe aortic stenosis in patients with advanced stages of renal insufficiency or dialysis therapy are still missing.