Functional Renal Failure Research Articles

Experience With Everolimus Following Calcineurin Inhibitor Withdrawal in Liver Transplant Recipients.

Background: Despite important contribution of calcineurin inhibition (CNI) in rejection prophylaxis, modern immunosuppressive protocols aim for CNI reduction or even withdrawal (WD) to prevent long-term CNI-associated nephrotoxicity. Early everolimus (EVR) introduction facilitated CNI reduction demonstrated superior renal function with comparable efficacy and safety profile. Here, we compare results from two CNI-WD arms tested in the H2304 and PROTECT liver transplant (LTx) studies. Methods: In H2304, patients randomized to CNI-WD (N=231) 1M after LTx, received EVR (C0 3-8 ng/mL) with reduced tacrolimus (TAC) (C0 3-5 ng/mL). By the end of M4, EVR was increased to C0 6-10 ng/mL and TAC was withdrawn. In PROTECT, recipients randomized at 4-8 weeks after LTx to CNI-WD (N=101), received EVR (C0 5-12 or 8-12 ng/mL with TAC or cyclosporine) with stepwise CNI reduction and complete withdrawal when patients were stable with 70% CNI reduction latest by M6 post-LTx; all patients received basilliximab induction. In the H2304 study, enrolment into the CNI-WD arm was stopped early due to higher acute rejection (AR) rate during CNI withdrawal. Both studies evaluated incidences of composite efficacy failure and evolution of renal function (GFR) with safety and tolerability at M12. Results: There were notable differences between both study protocols; e.g., induction therapy in PROTECT, initiation and EVR exposure, and time to CNI elimination. At M12, incidence of composite efficacy failure was higher in the TAC-WD arm in the H2304 study vs. TAC-C, while in PROTECT, it was similar for both arms. Significant renal function improvement in the CNI-WD arm was noted without any new safety signals in both studies (table). Conclusion: It is important to maintain optimal level of immunosuppression (IS) during conversion from CNI to EVR-based IS to reduce the risk of subsequent efficacy failure. However, stepwise CNI withdrawal after induction therapy within 4M after initiation of EVR can be achieved safely with the appropriate protocol.Table: No Caption available.DISCLOSURES:Fischer, L.: Grant/Research Support, Novartis and Astellas, Speaker's Bureau, Gilead Sciences, Other, Novartis, Advisory committee. Fung, J.: Speaker's Bureau, GSK, Other, BMS, Advisory Committee, Vital Therapies, Consultant. Metselaar, H.: Grant/Research Support, Astellas, Biotest and Novartis, Speaker's Bureau, Astellas, Biotest and Novartis. Kaiser, G.: Grant/Research Support, Novartis, Astellas, Roche, Pfizer, Other, Novartis, Astellas, Roche, Pfizer, Travel Support. Neuhaus, P.: Grant/Research Support, Astellas and Novartis. Dong, G.: Employee, Novartis. Junge, G.: Employee, Novartis.

Retroperitoneal fibrosis: a clinical and outcome analysis of 58 cases and review of literature

The purpose of the study was to investigate the clinical features and outcomes of retroperitoneal fibrosis (RPF). Fifty-eight RPF treatment cases in the First Affiliated Hospital of China Medical University were retrospectively analyzed, including clinical characteristics and laboratory data. RPF was found predominantly in elderly men with atypical clinical manifestations of back pain, abdominal pain, and lower limb edemas. In laboratory examinations, the acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein levels increased significantly. Renal function failure was frequently found in patients with urethral obstruction. All patients had retroperitoneal soft tissue shadows or urethral obstructions on computed tomography (CT) or magnetic resonance imaging (MRI), seven of which had histological diagnosis of idiopathic RPF. Forty-two patients received surgical interventions; 29 patients received medication treatment alone including corticosteroids, immunosuppressants, and tamoxifen; 17 patients received corticosteroids after surgical intervention. Surgery followed by medication was most effective for RPF. CT and MRI help to exclude secondary causes, but biopsy remains the gold standard for diagnosis. Long-term low-dose corticosteroids and immunosuppressants may prevent relapse of RPF.

The Traditional Japanese Medicine (Kampo) Boiogito has a Dual Benefit in Cardiorenal Syndrome : A Pilot Observational Study

Background:Conventional treatment for cardiorenal syndrome (CRS) is frequently associated with drug resistance and limited clinical success.We aimed to explore a new approach utilizing Boiogito (TJ-20), a traditional Japanese medicine(Kampo),in combination with conventional treatment for patients with CRS. Methods and Results:We enrolled 26 patients with CRS (18 men;mean age,77±8.4 years;mean serum brain natriuretic peptide(BNP),241.5±196.6 pg/mL;mean estimated glomerular filtration rate(eGFR),40.02±10.54 mL.min .1.73 m ). Treatment with TJ-20 was started at an average dose of 4.6±1.5 g/day, which was increased to 5.2±1.2 g/day at 3.5 months and to 5.9±1.5 g/day at 9.4 months.TJ-20 treatment significantly increased mean eGFR (mL.min .1.73 m )to 44.60±10.76 at 3.5 months (P=0.001),and to 45.93±11.57 at 9. 4 months (P=0.0004).In addition,the New York Heart Association functional classification improved (P=0. 019),and serum BNP levels decreased significantly to 195.5±145.7 pg/mL at 3.5 months(P=0.008)and to 163. 3±130.2 pg/mL at 9.4 months (P=0.007).The increase in eGFR had no correlation with the decrease in BNP level,indicating independent effects on both renal function and heart failure status. Conclusions:TJ-20 can benefit both renal function and heart failure status in patients with CRS.Alternative medicine utilizing TJ-20 may provide a novel and useful strategy for the difficult management of patients with CRS.Shinshu Med J 62 : 89―97, 2014 (Received for publication December 2,2013;accepted in revised form January 8,2014)

Beneficial neurohumoral profile in left ventricular systolic dysfunction following acute myocardial infarction

Abstract

Current Therapies for Hepatorenal Syndrome

Hepatorenal syndrome (HRS) is a feared common complication of patients with cirrhosis. This syndrome is mainly characterized by functional renal failure due to renal vasoconstriction in the absence of underlying kidney pathology. The pathogenesis of HRS is complex and a final result of an extreme underfilling of the arterial circulation secondary to an arterial vasodilation located in the splanchnic circulation. This phenomenon leads to a compensatory response with activation of vasoconstrictors that cause intense renal vasoconstriction and kidney failure. The diagnosis of HRS is based on established diagnostic criteria aimed at excluding nonfunctional causes of renal failure. However in recent years the diagnosis of renal failure in patients with cirrhosis has also been adapted to include the acute kidney injury criteria proposed by the acute kidney injury network. The prognosis of patients with HRS is poor, especially in those who have a rapidly progressive course. Liver transplantation is the best option in suitable candidates, but difficult to implement in all patients due to the poor prognosis of many patients. Pharmacological therapies based on the use of vasoconstrictor drugs plus intravenous albumins are the standard first line of therapy. Other treatments such as transjugular intrahepatic portosystemic shunts and renal replacement may be effective but experience is limited. HRS prophylaxisis recommended in patients with spontaneous bacterial peritonitis, advanced cirrhosis and those with severe acute alcoholic hepatitis.

Syndrome hépatorénal

Hepatorenal syndrome is a severe complication of end-stage liver disease. The pathophysiological hallmark is severe renal vasoconstriction, resulting from peripheral and splanchnic vasodilation as well as activation of renal vasoconstrictor molecules, which induce the effective arterial volume reduction and the functional renal failure. The diagnosis of hepatorenal syndrome is currently based on the exclusion of other causes of renal failure (especially prerenal). Spontaneous bacterial peritonitis is one of the triggering factors and should be sought in all patients with severe liver disease and acute renal failure. Quickly treating patients with parental antibiotics and albumin infusion significantly decreases the risk. The combined use of intravenous albumin, splanchnic and peripheral vasoconstrictor and/or renal replacement therapy sometimes enables a delay until liver transplantation (or combined liver–kidney in selected patients). Transplantation is in fact the only way to improve the long-term prognosis.

Anesthetic experience of a patient with Prune-belly syndrome.

Anesthetic experience of a patient with Prune-belly syndrome.

Biomarkers in heart failure.

Appropriate use of biomarkers is clinically important for identifying heart failure in its early stage, optimizing risk stratification, and managing patients. This article describes established and traditional biomarkers as well as novel biomarkers reflective of myocardial stress, myocardial damage, extracellular matrix, oxidative stress, inflammation, renal function, micro RNAs, and heart failure with preserved left ventricular ejection fraction. This review focuses on the recent advances in cardiac and non-cardiac biomarkers of heart failure and their appropriate use in clinical practice.

Biological pathways and potential targets for prevention and therapy of chronic allograft nephropathy.

Renal transplantation (RT) is the best option for patients with end-stage renal disease, but the half-life is limited to a decade due to progressive deterioration of renal function and transplant failure from chronic allograft nephropathy (CAN), which is the leading cause of transplant loss. Extensive research has been done to understand the pathogenesis, the biological pathways of fibrogenesis, and potential therapeutic targets for the prevention and treatment of CAN. Despite the advancements in the immunosuppressive agents and patient care, CAN continues to remain an unresolved problem in renal transplantation. The aim of this paper is to undertake a comprehensive review of the literature on the pathogenesis, biological pathways of RT fibrogenesis, and potential therapeutic targets for the prevention and therapy of CAN.

Correlation analysis of angiotensin-converting enzyme, angiotensinogen, and endothelial nitric oxide synthase gene polymorphisms and the progression of immunoglobulin A nephropathy/membranous nephropathy

The purpose of our study was to evaluate the correlation of polymorphisms in angiotensinogen (AGT), angiotensin-converting enzyme (ACE), and endothelial nitric oxide synthase (eNOS) genes and the development and prognostic implications for immunoglobulin A nephropathy (IgAN)/membranous nephropathy (MN). A polymerase chain reaction was performed for the AGT, ACE, and eNOS genes, followed by DNA sequencing and statistical analysis. There was a difference in ACE gene type II and type I between the IgAN and MN groups (P < .05) and in eNOS gene TT type and T type between the IgAN and MN groups (P < .05 and P < .01). In the IgAN group, significant differences were observed between ACE gene polymorphism and the age group of 20 years or less, male sex group, with/without hematuria, and high blood urea nitrogen (BUN; P < .05 or P < .01); between AGT gene polymorphism and with/without hematuria, high BUN, and pathologic classification (P < .05 or P < .01); and between eNOS gene polymorphism and high BUN and pathologic classification (P < .05 or P < .01). However, in the MN group, significant differences were observed between ACE gene polymorphism and the degree of proteinuria and high BUN (P < .001 and P < .05), between AGT gene polymorphism and with/without hematuria (P < .05), and between eNOS gene polymorphism and the degree of proteinuria and high BUN (P < .05 and P < .01). The ACE, AGT, and eNOS genes were correlated with the development of renal function failure in IgAN, whereas the ACE and eNOS genes were associated with the degree of proteinuria and the development of renal function failure in MN.

COL4A3/COL4A4 Mutations and Features in Individuals with Autosomal Recessive Alport Syndrome

Alport syndrome is an inherited disease characterized by hematuria, progressive renal failure, hearing loss, and ocular abnormalities. Autosomal recessive Alport syndrome is suspected in consanguineous families and when female patients develop renal failure. Fifteen percent of patients with Alport syndrome have autosomal recessive inheritance caused by two pathogenic mutations in either COL4A3 or COL4A4. Here, we describe the mutations and clinical features in 40 individuals including 9 children and 21 female individuals (53%) with autosomal recessive inheritance indicated by the detection of two mutations. The median age was 31 years (range, 6-54 years). The median age at end stage renal failure was 22.5 years (range, 10-38 years), but renal function was normal in nine adults (29%). Hearing loss and ocular abnormalities were common (23 of 35 patients [66%] and 10 of 18 patients [56%], respectively). Twenty mutation pairs (50%) affected COL4A3 and 20 pairs affected COL4A4. Of the 68 variants identified, 39 were novel, 12 were homozygous changes, and 9 were present in multiple individuals, including c.2906C>G (p.(Ser969*)) in COL4A4, which was found in 23% of the patients. Thirty-six variants (53%) resulted directly or indirectly in a stop codon, and all 17 individuals with early onset renal failure had at least one such mutation, whereas these mutations were less common in patients with normal renal function or late-onset renal failure. In conclusion, patient phenotypes may vary depending on the underlying mutations, and genetic testing should be considered for the routine diagnosis of autosomal recessive Alport syndrome.

Predictors of operative mortality following major lower extremity amputations using the National Surgical Quality Improvement Program public use data

The most definitive outcome data on lower extremity amputation (LEA) comes from the Veterans Administration (VA) system. Because of the unique nature of VA patients (more chronic disease, greater functional disability, and lower socioeconomic status), it is not clear these results can be generalized to the private sector. This study was undertaken to determine the short-term outcome of LEA in private sector patients and to define predictors of operative mortality. After Institutional Review Board approval and under the National Surgical Quality Improvement Program public use agreement, a data set of LEA based on Current Procedural Terminology coding was assembled for the years 2005 to 2008. Patient demographics, comorbidities, and laboratory values were compiled and linked to operative mortality. Dichotomous variables were analyzed using χ(2) test with odds ratios (ORs) and continuous variables with Student t-test. Predictive modeling was done using stepwise logistic regression. Data were analyzed in SPSS. A total of 6839 patients underwent 4001 amputations below-knee (BK) and 2838 above-knee (AK) with a 9.1% operative mortality (6.5% BK, 12.7% AK; P < .001). Age >60 years (OR, 2.4; 95% confidence interval [CI], 1.9-2.9), white race (OR, 1.2; 95% CI, 1.0-1.4), and American Society of Anesthesiologists classification (II, 2.3% vs IV, 13.8%) were significant predictors of mortality. Preoperative functional status (20% for totally dependent vs 4.3% for independent), renal failure (OR, 2.3; 95% CI, 1.7-3.2), and congestive heart failure (OR, 2.6; 95% CI, 2.1-3.3) also predicted death. Postoperative complications associated with mortality included pneumonia (OR, 5.4; 95% CI, 4.1-7.0), ventilator dependence (OR, 5.1; 95% CI, 3.8-6.8), and need for transfusion (OR, 3.7; 95% CI, 2.0-6.7). Hispanic and African-American race (OR, 0.6; 95% CI, 0.4-0.9 and OR, 0.8; 95% CI, 0.7-1), history of peripheral arterial disease (OR, 0.6; 95% CI, 0.5-0.8), and smoking (OR, 0.5; 95% CI, 0.4-0.7) were protective (all ORs had P values < .001). The mortality of LEA in private sector patients remains high, with risk factors similar to those identified in previous studies of VA patients. These results should serve as a benchmark for future attempts to improve the outcome of LEA and serve to improve patient and family counseling.

Preoperative Evaluation: Screening Using a Questionnaire

Background and objectivePrior to elective surgery it is essential to know in advance the patient's clinical condition. The aim of this study was to compare the preoperative evaluation (POE) through questionnaire responses with preanesthetic evaluation by the anesthesiologist. MethodPrior to their preoperative evaluation, patients answered a questionnaire with information regarding age, weight, height, scheduled surgery, past medical and surgical history, allergies, medications and doses used, social history (illicit drugs, alcohol, smoking), functional capacity and exercise tolerance. Preoperative evaluation was performed by an anesthesiologist who had no access to the questionnaire data or knowledge about the research. The questionnaire data were compared with the preoperative evaluation by two independent investigators, in order to answer the questions: 1) Was the questionnaire evaluation effective - could the patient undergo surgery without the need for face-to-face consultation? 2) Has been there any relevant information - ability to change the anesthetic approach - not assessed by the questionnaire, but assessed by the face-to-face consultation? 3) Has been there any information added by the health questionnaire that was missed by face-to-face consultation? For statistical analysis, the paired Student's t-test was used for parametric data and chi-square test for categorical data, with p < 0.05 considered significant. ResultsOf the 269 eligible patients there was one refusal, and four agreed to participate but did not complete the questionnaire, in addition to 52 losses, totaling 212 participants. Questionnaire data added to the consultation in 109 cases (51.4%). The screening questionnaire alone was effective for 144 patients (67.93%), with no need for consultation. The anesthesiologist evaluation referred patients for surgery on their first visit in 178 opportunities (84%). In the identification of cases of non-referral to surgery, the questionnaire showed a negative predictive value of 94.4%, positive predictive value of 38.2%, sensitivity of 76.5%, and specificity of 76.4%. Statistically significant (P < 0.05) clinical factors associated with non-referral to surgery were: age over 65 years, BMI > 30, low functional capacity, hypertension, diabetes mellitus, asthma, renal failure, hepatitis, and ischemic heart disease. ConclusionThe questionnaire was effective for screening patients who needed further evaluation and/or changes in treatment regimen prior to elective surgery. Moreover, the questionnaire added data not covered by clinical evaluation.

PWE-146 Relaxin Is a Renal Vasodilator in Experimental Models of Cirrhosis and A Potential Novel Therapy for Hepatorenal Syndrome in Humans

IntroductionHepatorenal syndrome (HRS) is a feared complication of cirrhosis with a high mortality rate and limited treatment options. The hallmark features of HRS are profound renal vasoconstriction, resulting in a...

Management experience of acute renal failure induced by unilateral ureteral calculi obstruction

To explore the causes and treatment options of acute renal failure induced by unilateral ureteral calculi obstruction. The clinical data of 12 cases of acute renal failure induced by unilateral ureteral calculi obstruction between August 2008 and July 2012 were reviewed retrospectively. There were 5 males and 7 females with an average age of 65.7 years. Their clinical data and treatment options were retrospectively analyzed and summarized. Seven cases showed right side ureteral calculus with hydronephrosis while another 5 presented left side ureteral calculus with hydronephrosis. Serum creatinine was higher than 310 µmol/L in 12 cases. Anuria appeared in 4 cases for 1-7 days while oliguria in 8 cases for 2-10 days. High fever was present in 11 cases, the highest of whom was 40 °C. White blood cell count increased in 10 cases (>10×10(9)/L) and decreased in 2 cases (<4 × 10(9)/L). The therapeutic options included insertion of double J stent for internal drainage (n = 1), percutaneous nephrostomy for external drainage (n = 10) and open operation (n = 1). Traditional treatments were performed to manage ureteral calculus in the above 11 cases with drainage. All cases had improved renal function after comprehensive treatment of anti-infection, antishock, rinsing stones and relieving obstruction. All 12 cases were treated successfully. Unilateral ureteral calculus may impair contralateral renal function and cause acute renal failure due to the absorption of toxin at obstructive side. The keys of management are eliminating toxin and relieving obstruction.

1024 RELAXIN IS A RENAL VASODILATOR IN EXPERIMENTAL MODELS OF CIRRHOSIS AND A POTENTIAL NOVEL THERAPY FOR HEPATORENAL SYNDROME (HRS) IN HUMANS

Background Hepatorenal syndrome is a feared complication of cirrhosis, with a high mortality rate and limited treatment options. The hallmarks of the disorder are functional renal failure, normal kidney histological findings, and profound renal vasoconstriction. The hormone relaxin mediates haemodynamic adaptations to pregnancy including increased renal blood flow and glomerular filtration rate (GFR). We hypothesised that relaxin could be used to modulate renal blood flow in cirrhosis.

ECMO as a Bridge to Decision in “Crash an Burn” Patients: 8-Years Experience

Purpose Treatment of refractory cardiogenic shock with VAD or transplantation is controversial. The aim of our study was to evaluate ECMO support as a bridge to decision in “crash and burn patients” through our 8-years experience. Methods and Materials From June 2003 to December 2011, 124 patients received an ECMO for refractory cardiogenic shock, 26 out-hospital cardiac arrests were excluded from our study. Median age was 43 years, range from 11 to 73 years. Primary diagnoses were postcardiotomy failure (29.6%), end stage heart failure (18.4%), acute ischemic cardiomyopathy (17.4%), primary graft failure (12.2%), myocarditis (5.1%) and others (17.3%). ECMO was used in in-hospital arrest in 37.8% of cases. Peripheral femoro-femoral ECMO was mainly implanted (79.6%), a “central ECMO” was used in 20 patients. Results The median duration of ECMO support was 4.5 days (12 hours to 82 days). Mortality while supported with ECMO was 50% (40 patients) with a median support time of 2 days. Weaning from ECMO was achieved through cardiac recovery (57.7%), heart transplantation (26.5%), VAD implantation (14.1%). Most of the patients were weaned between the 4th and the 11th days of support (87.5%). Survival was 82.7%, 61.5% and 71.4% in case of cardiac recovery, heart transplantation or VAD implantation respectively. Stroke and persistent renal function impairment were significant risk factors with OR: 4.940 [2.274– 10.732], p Conclusions ECMO brings promising results as a bridge to decision in end stage refractory cardiogenic shock patients. Persistent renal function failure while supported with ECMO was associated with poor outcome. Further studies are needed to build appropriate risks score to better determine issues for patients supported with ECMO.

Relaxin is a renal vasodilator in experimental models of cirrhosis and a potential novel therapy for hepatorenal syndrome in man

BackgroundHepatorenal syndrome is a feared complication of cirrhosis, with a high mortality rate and limited treatment options. The hallmarks of the disorder are functional renal failure, normal kidney histological findings, and profound renal vasoconstriction. The hormone relaxin mediates haemodynamic adaptations to pregnancy including increased renal blood flow and glomerular filtration rate (GFR). We hypothesised that relaxin could be used to modulate renal blood flow in cirrhosis. MethodsCirrhosis was induced in male rats by 16 weeks of carbon tetrachloride (intraperitoneally) and decompensated biliary cirrhosis by bile duct ligation. The effect of acute intravenous or extended (72 h) subcutaneous relaxin versus placebo was determined by analysis of systemic haemodynamics, renal blood flow, GFR, and organ histology. The effect of co-treatment with L-NG-nitroarginine methyl ester (L-NAME) was measured in subgroups of relaxin or placebo treated rats. Blood oxygen dependent-MRI (BOLD-MRI) was used to non-invasively detect changes to renal oxygenation. Hepatic and renal expression of RXFP1 (relaxin receptor) was determined by IHC and quantitative PCR (qPCR). A qPCR array was used to quantify changes in renal vasodilator/vasoconstrictor gene expression in response to relaxin. FindingsRXFP1 was detected in glomerular podocytes, renal pericytes, and renal, segmental, and interlobar arteries of cirrhotic rats. In carbon tetrachloride (CCl4) induced cirrhosis, acute intravenous relaxin (4 μg) induced a 50% increase in renal blood flow after 60 min (p<0·01 vs placebo, n=6). BOLD-MRI showed statistically significant (p<0·05) increased tissue oxygenation at the same timepoint in renal cortex and medulla. Extended subcutaneous relaxin increased renal blood flow by 54% in CCl4 (p<0·01 vs placebo, n=8) and 87% in bile duct ligated animals (p<0·05 vs placebo, n=3) and increased GFR by 138% in CCl 4 (p<0·01 vs placebo, n=8) and 70% in bile duct ligated animals (p<0·05 vs placebo, n=3). Mean arterial pressure was unaffected by relaxin. L-NAME (250 mg/L) orally abrogated the effect of relaxin on renal blood flow and GFR. Relative expression of vasoconstrictor genes in kidney was markedly reduced by relaxin treatment. InterpretationRelaxin increases renal blood flow in experimental models of cirrhosis. Crucially, relaxin also improves renal function and oxygenation and does not induce systemic hypotension even in advanced disease. These effects are modulated via augmentation of nitric oxide and downregulation of vasoconstrictors, pivotal in the pathogenesis of hepatorenal syndrome. Relaxin has potential as a novel therapy for hepatorenal syndrome, and further translational studies are warranted. FundingWellcome Trust through the Scottish Translational Medicine and Therapeutics Initiative.

The role of co-morbidity in the selection of antidiabetic pharmacotherapy in type-2 diabetes

Metformin is, if not contraindicated and if tolerated, usually preferred over other antidiabetic drugs for the first line treatment of type-2 diabetes. The particular decision on which antidiabetic agent to use is based on variables such as efficacy, cost, potential side effects, effects on weight, comorbidities, hypoglycemia, risk, and patient preferences. However, there is no guidance how to consider these in the selection of antidiabetic drug treatment. In this work, we aimed to summarize available evidence and tried to give pragmatic treatment recommendations from a clinical practice perspective.There are clear contraindications for some drugs in those with impaired renal and liver function and precautions in those with heart failure for the use of metformin (NYHA III-IV) and glitazones. On the other hand, GLP-1 analogs, DPP-4 inhibitors and acarbose are generally less critical and can be used in the majority of patients. We identified the following gaps with respect to the selection of antidiabetic drug treatment in patients with co-morbid disease conditions: 1) Guidelines fail to give advice on the use of specific antidiabetic drugs in patients with co-morbidity. 2) The literature is deficient in studies documenting antidiabetic drug use in patients with severely impaired renal function, diabetic retinopathy, cerebrovascular disease and systolic heart failure. 3) Further there are no specific data on patients with multiple of these co-morbid disease conditions. We postulate that differential use of antidiabetic drugs in patients with co-morbid disease constellations will help to reduce treatment related complications and might improve prognosis.

First-in-human use of the OneShot™ renal denervation system from Covidien

Percutaneous transcatheter renal sympathetic denervation (RDN) is a promising treatment for refractory hypertension (HT). RDN was found in one series of clinical studies to reduce systolic blood pressure (SBP) by as much as a mean of 30 mmHg with 85% of subjects experiencing sustained reductions of 10 mm or more out to two years after RDN. This degree of blood pressure reduction may reduce stroke and myocardial infarction rates and is anticipated to translate into improved life expectancy. The lowering of blood pressure by RDN has been shown to improve glycaemic control and reverse left ventricular hypertrophy. Beneficial effects on renal function, sleep apnoea and heart failure are suggested as well. This report describes the first patient treated using the OneShot™ Renal Denervation System (formerly Maya Medical now Covidien, Campbell, CA, USA).