Concomitant Renal Disease Research Articles

A rare deleterious case of concomitant renal disease associated with IgG4-associated systemic disease

In IgG4-associated disease, several organs and tissues are often affected, especially kidney tissue, and is characterized by interstitial nephritis, obstructive nephropathy, and in rare cases glomerulopathy (including membra[1]nous nephropathy).IgG4-associated disease was isolated as an independent nosological form in 2003, when patients with type 1 autoimmune pancreatitis were found signs of systemic damage (involvement of the biliary tract, salivary glands, retroperitoneal space), and in 2012 the first international nomenclature of the disease was proposed.The clinical manifestations of IgG4-associated disease are nonspecific and diverse, which determines the difficulties of differential diagnosis, including infections and tumors, and increases the period from the onset of the disease to diagnosis to an average of 2 years. IgG4-associated disease is more likely to develop in middle age and old age. The prevalence of the disease is higher among men than among women. Thus, autoimmune pancreatitis type 1, retroperitoneal fibrosis and tubulointerstitial nephritis are more common in men, and sialoadenitis, dacryoadenitis and thyroiditis are more common in women.In this article, we present a clinical case of IgG4-associated systemic disease with a combined lesion of the tubulo-interstitial and glomerular compartments of kidney tissue with nephrotic syndrome as the only initial manifestation. The combination of IgG4-tubulo-interstitial nephritis with membranous nephropathy is an ex[1]tremely rare pathology. Nephrobiopsy was crucial in the diagnosis of this condition, which allowed the patient to be prescribed proper and timely treatment.

Echocardiographic findings in subjects with an amyloidogenic apolipoprotein A1 pathogenic variant

Background Very small case series of patients with apolipoprotein A1 (ApoA1) amyloidosis are available. Methods We described the clinical and echocardiographic characteristics of individuals with the pathogenic APOA1 variant Leu75Pro (p. Leu99Pro), referred for cardiac screening. Results We enrolled 189 subjects, 54% men, median age 55 years (interquartile range 42–67), 39% with concomitant renal disease and 31% with liver disease. Median left ventricular ejection fraction was 60% (55–66). Overall, these subjects did not show overt diastolic dysfunction nor left ventricular (LV) hypertrophy. Age correlated with interventricular septal (IVS) thickness (r = 0.484), LV mass index (r = 0.459), E/e’ (r = 0.501), and right ventricular free wall thickness (r = 0.594) (all p < 0.001). Some individuals displayed red flags for cardiac amyloidosis (CA), and 14% met non-invasive criteria for CA. Twenty-nine subjects died over 5.8 years (4.1–8.0), with 10 deaths for cardiovascular causes. Individuals meeting echocardiographic criteria for CA had a much higher risk of all-cause death (p = 0.009), cardiovascular death (p = 0.001), cardiovascular death or heart failure (HF) hospitalisation (p < 0.001). Subjects with both renal and liver involvement had a more prominent cardiac involvement, and shortest survival. Conclusions Subjects with the APOA1 Leu75Pro variant displayed minor echocardiographic signs of cardiac involvement, but 14% met echocardiographic criteria for CA. Subjects with suspected CA had a worse outcome.

Risk factors for 30-day readmission following liver transplantation in Pennsylvania

BackgroundReadmissions after liver transplantation (LT) are common given the complexity of the procedure, the severity of illness of patients, and complications related to immunosuppression. The objectives of this research were to identify risk factors for 30-day readmission and length of stay (LOS) for patients undergoing LT in Pennsylvania (PA). MethodsData from the Pennsylvania Health Care Cost Containment Council (PHC4) were used to identify 1,163 patients admitted to 10 liver transplant centers in Pennsylvania for liver transplantation between 2010 and 2018. Logistic and generalized linear regression models were used to estimate risk factors for 30-day readmission and LOS, respectively, adjusting for patient, disease, and hospital characteristics. ResultsOf the 1,163 patients receiving LT, 361 (31.1%) required readmission within 30 days, most frequently for surgical complication (23.5%). Both 30-day readmission rates and LOS showed a decreasing trend from 2010 to 2018. Readmitted patients were more likely to be younger than 60, female, have had a longer LOS, have been discharged to a skilled nursing facility, and have concomitant comorbid renal disease. Longer LOS was associated with patients who had an emergent admission, were transferred from another acute care institution, had surgical complications, and were discharged to a skilled nursing facility. We also found that age, hospital volume, and comorbidities were associated with longer LOS. ConclusionsPatient demographics, including age, sex, and race/ethnicity are associated with readmission and LOS following LT in PA. These results may be useful in guiding efforts to prevent readmissions.

Basic nephropathology for pathologists-part1 : Kidney biopsy-inflammation and immune complexes

The assessment of kidney biopsies is mainly confined to specialized centres. However, sometimes akidney biopsy is submitted to ageneral pathologist, and in addition peritumorous renal parenchyma in tumour nephrectomies can have concomitant non-neoplastic renal disease. Here we present asurvey of inflammatory and immunologic changes in all renal compartments, which may in part indicate the need of prompt therapeutic intervention such as in vasculitis, glomerulonephritis and interstitial nephritis. It is important to take into account that renal involvement of vasculitis is mainly centred in glomeruli and only to amuch lesser extent in arteries, and that the frequently observed interstitial inflammation very often is an epiphenomenon of another primary kidney disease and not an independent disease process. Typical renal patterns of injury are emphasised.

Chronic Renal Failure and Cardiovascular Disease: A Comprehensive Appraisal.

Coronary artery disease is highly prevalent in patients with chronic kidney disease. The concomitant renal disease often poses a major challenge in decision making as symptoms, cardiac biomarkers and noninvasive studies for evaluation of myocardial ischemia have different sensitivity and specificity thresholds in this specific population. Moreover, the effectiveness and safety of intervention and medical treatment in those patients is of great doubt as most clinical studies exclude patients with advance CKD. In the present paper, we discuss and review the literature in the diagnosis, treatment and prevention of CAD in the acute and chronic setting, in patients with CKD.

Risk of death with sodium-glucose co-transporter-2 inhibitors across the hallmark cardiovascular and renal outcome trials: an updated meta-analysis

Abstract Background Patients with type 2 diabetes mellitus (T2DM) experience a 15% increase in the risk for death compared to the general population, with age less than 55 years, insufficient glycemic control and albuminuria representing the major risk factors for all-cause and cardiovascular mortality. Despite progression in diagnosis and treatment, mortality remains elevated among affected individuals. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors are considered as the optimal treatment option for patients with T2DM and concomitant cardiovascular or renal disease, while these regimens demonstrated a clear benefit in all-cause and cardiovascular mortality compared to placebo. Purpose As we recently welcomed the publication of large-scale randomized controlled trials (RCTs) with SGLT-2 inhibitors addressing surrogate, hard endpoints, we sought to perform an updated meta-analysis, investigating the effect of SGLT-2 inhibitors on all-cause, cardiovascular and renal death among the high- or very-high risk patients enrolled in those trials. Methods We pooled data from the relevant, recent hallmark RCTs; 10 trials were included in our analysis encompassing a total of 71,533 enrolled participants, assigned either to SGLT-2 inhibitor treatment or placebo. We set cardiovascular death as the primary efficacy outcome, while we assessed all-cause death and renal death as secondary efficacy outcomes. Results Treatment with SGLT-2 inhibitors resulted in a significant decrease in the risk of cardiovascular death, equal to 14% (RR = 0.86, 95% CI; 0.80 to 0.93, I2=22%). Only canagliflozin produced a significant result, while dapagliflozin led to a marginally non-significant reduction in cardiovascular mortality (Figure 1). Notably, SGLT-2 inhibitors led to a significant decrease in the risk for all-cause death, equal to 14% (RR=0.86, 95% CI; 0.81 to 0.92, I2=34%) the result was significant only for canagliflozin and dapagliflozin, while none of the rest SGLT-2 inhibitors resulted in a significant decrease in the risk for all-cause death (Figure 1). SGLT-2 inhibitors also produced a non-significant decrease in the risk for renal death (RR=0.36, 95% CI; 0.12 to 1.14, I2=0%). Neither canagliflozin nor dapagliflozin had a significant impact on risk reduction for renal death, while no cases of renal death were reported in VERTIS CV trial. No subgroup differences were identified for any of the three comparisons (Figure 2). Conclusions Antidiabetic treatment with SGLT-2 inhibitors provides a clear benefit in terms of cardiovascular and all-cause mortality for the very high-risk patients enrolled in the cardiovascular and renal outcome trials. Canagliflozin seems to be associated with the greatest impact on risk reduction for all-cause and cardiovascular death, followed by dapagliflozin. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Real-world safety and effectiveness of nivolumab in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction cancer that has progressed after chemotherapy: a postmarketing surveillance study

BackgroundThis postmarketing surveillance study evaluated the real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer.MethodsThis multicenter, observational study was conducted at 158 centers in Japan. Patients with unresectable advanced or recurrent G/GEJ cancer were registered between Nov 1, 2017, and Oct 31, 2018, and observed for 6 months after treatment initiation with nivolumab. Correlation of background characteristics with treatment-related adverse events (TRAEs) and tumor response was explored.ResultsOverall, 654 patients were registered (safety analysis set, n = 650; effectiveness analysis set, n = 636; response evaluation set, n = 516). The incidences of all TRAEs and grade ≥ 3 TRAEs were 31.5 and 11.2%, respectively. TRAEs significantly correlated with the absence of peritoneal metastasis; C-reactive protein level < 1; prior G/GEJ cancer surgery; and past or concomitant pulmonary, thyroid, or renal disease (each p < 0.05). The incidence of TRAEs was significantly lower in patients with higher Glasgow prognostic scores (p < 0.05). No new safety signals were observed. Complete response, partial response, stable disease, and progressive disease were observed in 1.2, 10.1, 27.1, and 58.3% of the response evaluation set, respectively. Patients aged ≥ 65 years (13.9 vs 5.3%, p = 0.0083) and ≥ 75 years (18.8 vs 9.2%, p = 0.0036) showed a higher response rate than their younger counterparts.ConclusionsThe real-world safety and effectiveness of nivolumab as salvage (after ≥ 2 lines) therapy in Japanese patients with unresectable advanced or recurrent G/GEJ cancer were consistent with those observed in the phase 3 ATTRACTION-2 study.

Strategies that Reduce Post-endoscopic Submucosal Dissection Bleeding

Bleeding after endoscopic submucosal dissection (ESD), one of the most common postprocedural adverse events, is the main cause of increased readmission rates and hospital costs. Generally, the incidence of post-ESD bleeding is estimated to be about 5%. However, the incidence of bleeding is particularly increased in high-risk patients. In particular, it has an incidence of over 50% in patients that use antithrombotic agents. The well-known risk factors for post-ESD bleeding include antithrombotic therapy, lesions in the proximal stomach, specimen size &gt;4 cm, and concomitant renal disease. Currently, the number of patients at a high risk of post-ESD bleeding has been increasing. This may be due to the aging society and the increase in the usage of antithrombotic agents. Therefore, several strategies have been employed to prevent post-ESD bleeding. These strategies include acid inhibition therapy, preventive hemostasis using Doppler endoscopic ultrasound and artery-selective clipping, second look endoscopy, the closings method, and the shield methods. However, these methods are technically demanding, which hinders their wide usage in clinical practice. Recently, several hemostatic powders have been developed and clinically used in the treatment of gastrointestinal bleeding. In this article, we review the risk factors for post-ESD bleeding and the recently introduced prevention methods. Moreover, we aimed to explore realistic and appropriate strategies for the prevention of post-ESD bleeding.

Clinical and Sociodemographic Profile of Patients With Thyroid Storm: A National Inpatient Sample Database Analysis

Background: Thyroid storm (TS) is a rare, life-threatening disease that is associated with significant mortality. The clinical outcome of these patients has not been evaluated in general practice on a national scale. Our study aimed to find the clinical characteristics and outcomes of patients admitted to community hospitals with TS using the National Inpatient Sample (NIS) database. Methods: We conducted a retrospective study of adult patients (>=18 years of age) diagnosed with primary and secondary TS from the NIS database from 2012 to 2014. The NIS is the largest all-payer inpatient care database in the United States, containing data on more than seven million hospital stays each year. Statistical analysis performed included Chi-Square test, Wilcoxon two-sample test, Fisher’s exact test and multiple logistic regression with a p-value<0.05 considered significant. Results: In total, 2,163 hospitalizations with TS were identified. The incidence of TS in hospitalized patients was 11.96 per 100,000 hospitalizations. Compared to all other adult hospitalizations reported over the same period, admission with TS was significantly associated with a higher prevalence in African Americans (31.4% vs 14.7%, p<0.001) as well as concomitant blood diseases (31.4% vs 21.9%, p<0.001), drug use disorder (11.4% vs 8.4%, p<0.001), electrolyte disturbance (36.9% vs 23.8%, p<0.001), and psychosis (38.1% vs 28.5%, p<0.001). Admission with TS was associated with lower prevalence of concomitant cancer (2.5% vs 4.9%, p<0.001) and renal disease (5.6% vs 12.2%, p<0.001), along with a higher risk of death during hospitalization (3.9% vs 2.2%, p<0.001). There was no significant association between TS and GI disease, cardiovascular disease, pulmonary disease or rheumatoid arthritis. Admission with TS was associated with longer average length of stay (TS median: 4 days, Non-TS: 3 days, p<0.001) and higher total hospital charge (TS median: $27,360, Non-TS: $24,346, p<0.001). Additionally, TS had a higher incidence in urban populations with large hospitals.Overall, inpatient mortality rate was 3.9%. For those with TS, the odds of inpatient death were greater for age group 30-59 compared to <30 (OR 2.916, p=0.026), age group >60 compared to <30 (OR 3.157, p=0.022), males (OR 2.20, p<0.001), those with cancer (OR 6.42, p<0.001), those with electrolyte disturbance (OR 6.12, p<0.001) and those with a neurologic disorder (OR 2.46, p=0.002). Admitted patients with a concomitant psychological disorder had lower odds of death (OR 0.38, p=0.03). Conclusions: This study identified clinical characteristics associated with TS-related admission including female gender, age 30-59, Caucasian race, and urban populations. Higher mortality was associated with patients 30-59 years and >60 years of age, electrolyte disturbances, blood disease, weight loss, paralysis, cancer, renal disease, and male gender.

A Clinical Case: the Risk Factors of Acute Kidney Injury in a Cardiological Patient

Recent epidemiological studies have demonstrated that the development of a potentially reversible moderate acute kidney injury is associated with worsening clinical outcomes and an increased risk of death. This is especially true for patients with plural comorbidities who require procedures with IV radiopaque agents. This paper presents a clinical case of an elderly patient who requires coronary angiography, and who has common clinical conditions such as hypertension, multifocal atherosclerosis with the development of renal artery disease and the presence of a history of acute cerebrovascular accident and myocardial infarction, and chronic heart failure as well. Particular attention is given to assessing the risk of developing contrast-induced acute kidney injury in patients with cardiovascular disease, as well as discussing current views on the possibility of prescribing drugs that affect the reninangiotensin system in cardiac patients with concomitant renal artery disease.

Effects of Systemic Profiles on Choroidal Thickness in Treatment-Naïve Eyes With Diabetic Retinopathy.

PurposeThe purpose of this study was to analyze the effects of systemic and ocular profiles on subfoveal choroidal thickness (SFChT) in treatment-naïve eyes with diabetic retinopathy (DR).MethodsThis study included patients with treatment-naïve DR. They underwent routine laboratory evaluations, including complete blood cell count, liver function tests, kidney function tests, and urinalysis for macroalbuminuria. The systemic and ocular factors associated with the change in SFChT in DR were analyzed.ResultsA total of 136 eyes from 136 patients with diabetes and 30 eyes from 30 age-matched healthy controls were recruited. Generalized linear model analyses showed that the SFChT in treatment-naïve eyes with DR was positively associated with the DR grade and estimated glomerular filtration rate (eGFR; P = 0.001) and negatively associated with age (P < 0.001) and serum phosphorus levels (P = 0.001). Treatment-naïve eyes with proliferative DR (PDR; 313.4 ± 9.0 µm) or severe nonproliferative DR (NPDR; 299.7 ± 9.7 µm) had thicker choroid than eyes with mild to moderate NPDR (251.7 ± 11.1 µm) or no DR (231.2 ± 14.5 µm) after adjusting for age, eGFR, and phosphorus levels.ConclusionsChoroid is affected by renal function and the grade of DR in patients with diabetes. Advanced retinopathy is associated with choroidal thickening, and the severity of concomitant renal disease is associated with choroidal thinning.

SAT-374 The Many Faces of Parathyroid Carcinoma in the Philippines: A Case Series

Introduction: Parathyroid carcinoma is rare, affecting less than 1% of patients with primary hyperparathyroidism (PHPT). 1 Parathyroid carcinoma with concomitant papillary thyroid carcinoma is also rare, and the etiology is not fully defined. Clinical Case: We present 3 patients with parathyroid carcinoma and discuss their presenting symptoms, characteristics, and treatment. Two women and 1 man (2 Filipinos and 1 Marshallese) with age range 53-68 years old had parathyroid carcinoma. Two had primary hyperparathyroidism, one had non-functioning type of parathyroid carcinoma. Two had concomitant bone or renal disease. All three had concurrent thyroid disease- 2 had papillary thyroid microcarcinoma, one had colloid goiter. Because each one had different indications for neck surgery, different surgical techniques were done. Parathyroid cancer size ranged from 2.0-5.2 cm, with capsular and vascular invasion in all three. One case had double parathyroid carcinoma. No lymph node metastasis was identified. On follow up, the patient with the largest tumor size had tumor recurrence within 1 year from surgery. Conclusion: To the best of our knowledge, this is the first case series on parathyroid carcinoma in the Philippines, and includes the 7th case of double parathyroid carcinoma worldwide. Parathyroid carcinoma is a rare condition, and coupled with its highly variable presentation, as seen in the 3 cases, presents clinicians with a difficulty in arriving at a diagnosis. Histopathology remains the gold standard in diagnosis and is a key in guiding management. Since coexisting thyroid and parathyroid disease may occur, thyroid pathology should be evaluated in the presence of PHPT.

The Usage Of Plants as a Traditional and Complementary Medicine Among Diabetic Patients in Karachi, Pakistan: an Urgent Need of Educational İntervention

A one-month cross-sectional and questionnaire-based study was carried out in a government-based teaching hospital in Peshawar (Pakistan) during January 2019. Adult population having diabetes and interact with CAM for treatment purposes were approached. The simple random sampling technique was used for the participant's enrollment. A participant has a full choice to accept or reject to participate in the study. All the information collected via a validated questionnaire and then data were entered into the Statistical Package for Social Sciences (SPSS) for further analysis.A total of 100 individuals was investigated during the study period. The sample were mostly male (n= 62), came from rural (n= 77), aged group 30-59 years (n= 83), and 56 patients had Illiterate status. The ratio of type-2 patients (n=89) was higher than as compared to type-1 DM patients (n=11). Out of these patients the prevalence of clinical characteristic included anxiety (47.1%), chronic pain (33.9%), arthritis (30.6%), concomitant heart disease (20.7%), digestive problems (22.3%), renal disease (15.7%) and allergies (4.1%).More patients (n=68) considered conventional therapy more effective for diabetes, while 7 reported CAM and 25 favored CAM plus conventional treatment strategies. About 5% of the patients completely better, 35 reported satisfactory improvement and 60 reported no change after CAM usage for diabetes. Out of all the patients, 47 patients recommend CAM usage, however, 53 didn’t in favor CAM utilization in the treatment of DM.Caralluma tuberculata (n= 11), Solanum surrattens Burm.f. (n= 10), Fagoniacretica (n= 6), Justicia adhatoda (n= 6), Consolida ambigua (n= 5), Vernonia amydalina (n= 4), A. ParvifloraBenth (n=3), Nigella sativa (n= 3), Carumcarvi (n=2), Brberis lycium Royle (n=2), Trigonellaemodi Both. (n= 2), Abelmoschus esculentus (n=2) and Citruluscolocynthis (n=2) were the most frequently CAM products. The patients further reported that, these CAM products were freely available at low cost and most often recommended by a friend, neighbor, relative and Hakeem. Another interesting fact was that, ethno medicinal local plants in Pakistan such as, Caralluma tuberculata and Solanum surrattens Burm.f. were the most frequently used CAM and highest satisfaction level among DM patients. The use of CAM products among the adult DM patients was reported in this study. The different type of attitudes, perception and beliefs towards CAM was also revealed. The patients did not report any side effects of CAM use for treatment of DM, but adverse events and side effects have been well reported previously, hence, further empirical-evidence should require and necessary about guidance on the safe and appropriate use of CAM.

Retrograde Intrarenal Surgery Following Laser Endopyelotomy; Sequential Procedures for Ureteropelvic Junction Obstruction and Nephrolithiasis.

This study was designed to evaluate the effectiveness and safety of retrograde intrarenal surgery (RIRS)following retrograde laser endopyelotomy (rLEP) in concomitant ureteropelvic junction obstruction (UPJO) andstone disease. Patients with concomitant UPJO and renal stone disease who were first treated in ourclinic by rLEP for obstruction and then RIRS for stone disease were enrolled. Study period went from 2012 to2017. RIRS following rLEP was performed earliest at the sixth week. Patients who underwent rLEP were matchedwith those with normal anatomy at a 1:1 ratio based on the propensity scores. Additionally, clinical results werecompared in order to evaluate the effects of rLEP surgery on RIRS. Subsequently, patients who underwent RIRSfollowing rLEP were independently evaluated and factors affecting the success of sequential procedures wereinvestigated. The sole difference between those that underwent RIRS following rLEP (n=27) and controls with normalanatomy that underwent RIRS was in operative times (p = .011). Evaluation of potential success factors inthe sequential rLEP-RIRS group revealed that primary etiology, obstruction length less than 1cm, smaller stonesize and presence of single stone showed significant effects (p = .047, p = .030, p = .040, p ? .001, respectively).RIRS following rLEP generated an 81.5% stone-free and, after a median follow-up time of 32 months, a 74.1%obstruction-free rate. RIRS following rLEP in patients with UPJO and renal stones is an effective treatment method. It canbe used safely in patients with single stones < 2cm, short obstruction lengths, and presence of primary etiology.

SUN-LB015 Baseline Characteristics and Effects on CV and Kidney Outcomes with Linagliptin Versus Placebo, Across GFR Categories in CARMELINA

People with type 2 diabetes (T2D) with concomitant chronic kidney disease (CKD) and cardiovascular (CV) disease are at increased risk for recurrent CV events and hypoglycemia. Treatment of these individuals is clinically challenging, where the evidence-base for safety and efficacy of glucose lowering drugs is scarce, in particular in GFR categories G3b (eGFR 30-44 ml/min/1.73m2), G4 (eGFR < 30) and G5 (eGFR < 15). We analyzed baseline characteristics and effects on CV and kidney outcomes with the DPP-4 inhibitor linagliptin (LINA) vs. placebo (PBO), across GFR categories in CARMELINA (NCT01897532). People with T2D and either i) UACR >30 mg/g with concomitant CV disease, or ii) eGFR <45 ml/min/1.73m² regardless of UACR, or eGFR ≥45 - 75mL/min/1.73m² and UACR > 200 mg/g, were randomized to LINA 5 mg or placebo (PBO) q.d. in a double-blind fashion. The primary outcome was first occurrence of CV death, non-fatal myocardial infarction, or non-fatal stroke (3P-MACE), with an adjudicated secondary composite outcome of ESKD, renal death, or sustained ≥40% decrease in eGFR from baseline. Other adjudicated outcomes included hospitalized heart failure (hHF) and the 3P-MACE components. Subgroup-effects across GFR categories (G≤2, G3a, G3b and G≥4) were also assessed. Of the 6979 participants, 15.2% were in GFR category G≥4, 27.8% G3b, 19.3% G3a, and 37.7% G≤2 at baseline. Participants in G≥4 (mean±SD eGFR 23.4±4.2 mL/min/1.73m²) or G3b (eGFR 37.2±4.1) as compared with G3a (eGFR 51.4±4.4) and G≤2 (eGFR 81.6±16.7) had more albuminuria, longer T2D duration and were more frequently treated with insulin, but less often with sulfonylureas and metformin. Over a median 2.2 years, LINA did not affect the risk for 3P-MACE (HR.1.02 [95% CI, 0.89, 1.17]), the secondary kidney composite outcome (1.04 [0.89, 1.22]), hHF (0.90 [0.74, 1.08]), or CV mortality (0.96 [0.81, 1.14]). Incidences were higher by declining kidney function, e.g. the 3P-MACE PBO incidence rate was 2.4 fold higher in G≥4 (9.6 per 100 patient-yrs) relative to G≤2 (4.0 per 100-patient yrs), whereas the kidney composite 9.8 fold (14.7 vs 1.5 per 100 patient-yrs), hHF 4.1 fold (6.2 vs 1.5 per patient-yrs) and CV death 3.0 fold (6.8 vs 2.3 per 100 patient-yrs) higher, respectively. A consistent neutral effect was observed across all GFR categories (interaction p-values: 0.84 [3P-MACE], 0.36 [kidney composite], 0.88 [hHF], 0.23 [CV mortality]). Adverse events (AE) increased with declining kidney function, but the proportion with ≥1 AE, or ≥1 serious AE were balanced between LINA and PBO across the GFR categories. HbA1c was reduced significantly, but without increased risk for hypoglycemia with LINA vs PBO, across all GFR categories. These findings in a large, international CV outcome trial in patients with T2D and concomitant CV and renal disease support the safety and tolerability of LINA as a T2D therapy that can be used across a broad range of kidney disease. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Calprotectin in pregnancy and pregnancy-associated diseases: a systematic review and prospective cohort study.

Calprotectin, a marker of acute and chronic inflammation, may play a role in pregnancy-associated disorders. We aimed to summarize available clinical data on calprotectin in pregnancy and to establish normal values of calprotectin during the course of pregnancy. We performed a systematic review of the databases PubMed and Cochrane Central Register of Controlled Trials to identify experimental and clinical evidence assessing the role of calprotectin in pregnancy. In addition, we performed a prospective cohort study assessing serum and urine calprotectin throughout pregnancy. We identified 17 studies investigating 1638 pregnant women, 151 newborns, and 99 non-pregnant controls, measuring calprotectin in different compartments. Calprotectin was present in meconium and elevated in fecal samples of pregnant women with active inflammatory bowel disease. In women with pregnancy-induced hypertension, mild and severe preeclampsia (PE), calprotectin was significantly elevated in maternal plasma and serum, but not in fetal serum, amniotic fluid, and umbilical cord blood. For the cohort study, we recruited 196 pregnant women. PE and concomitant renal disease were present in 6/196 (3%) and 11/196 (5.6%) of women, respectively. Throughout pregnancy, median serum and urine levels of calprotectin largely exceed reported concentrations of the healthy non-pregnant population, but showed no significant variations between trimesters 1-3 and post-partum. Calprotectin in serum was correlated with systolic blood pressure and in urine with leukocytes and total protein. No significant differences were found in subgroup analyses of smokers vs. non-smokers, PE vs. none, and renal disease (kidney stones, reflux) vs. none. Calprotectin concentrations in amnion fluid and stools serve as potential indicators of inflammatory states during pregnancy. Urinary calprotectin concentrations are continuously high during pregnancy and show no significant variations between trimesters 1-3 and post-partum.

Association of renal artery stenosis with left ventricular remodeling in patients coexisting with renovascular and coronary artery disease.

Data about renal artery stenosis association with left ventricular remodeling in patients coexisting with coronary artery disease are scanty. Patients with suspected both coronary artery disease and renal artery stenosis undergoing coronary and renal arteriography between October 2013 and December 2015 were prospectively enrolled. Left ventricular remodeling patterns were compared among different severity of renal artery stenosis group. Logistic regression was done to investigate the determinants of the left ventricular morphology. The overall prevalence of left ventricular hypertrophy was 40.5%, the highest in bilateral renal artery stenosis group compared to unilateral or normal ones (65.4% versus 41.8% versus 34.8%, p = 0.012). Significantly lower estimated glomerular filtration rate and higher cystatin C level were found in bilateral renal artery stenosis group than that in other two groups. Multivariate regression analysis showed that bilateral renal artery stenosis was associated with increased left ventricular hypertrophy and concentric hypertrophy with statistical significance (adjusted odds ratio = 2.909 (95%CI: 1.063-7.961), and 3.021 (95%CI: 1.136-8.033)). In addition, estimated glomerular filtration rate level was also related to left ventricular hypertrophy, while there was no significant interaction between renal artery stenosis and coronary artery disease on left ventricular hypertrophy/concentric hypertrophy occurrence. Bilateral renal artery stenosis is significantly associated with increased left ventricular hypertrophy/concentric hypertrophy in patients with suspected concomitant coronary and renal artery disease, while no synergic effect could be found in coronary artery disease.

SOCS1-targeted therapy ameliorates renal and vascular oxidative stress in diabetes via STAT1 and PI3K inhibition

Oxidative stress resulting from excessive production of reactive oxygen species (ROS) or impaired antioxidant defenses is closely related to the development of diabetic vascular complications, including nephropathy and atherosclerosis. Chronic activation of Janus kinase/Signal transducer and activator of transcription (JAK/STAT) signaling pathway contributes to diabetic complications by inducing expression of genes involved in cell proliferation, fibrosis, inflammation, and oxidative stress. Suppressors of cytokine signaling (SOCS) family of endogenous JAK/STAT regulators is an attractive target for therapeutic intervention. We investigated the beneficial effect of two different SOCS1-targeted therapies (adenovirus-mediated gene transfer and kinase-inhibitory region peptidomimetic) to combat oxidative stress injury in an experimental diabetes model of concomitant renal and macrovascular disease (streptozotocin-induced diabetic apolipoprotein E-deficient mouse). Diabetes resulted in progressive alteration of redox balance in mice, as demonstrated by increased ROS levels and decreased antioxidant activity, which ultimately led to renal dysfunction and vascular injury. The molecular and pathological alterations in early diabetes were partially reversed by preventive intervention with SOCS1-targeted therapies. Importantly, SOCS1 peptidomimetic provided reno- and atheroprotection in diabetic mice even in a setting of established disease. Compared with untreated controls, kidney and aorta from SOCS1-treated mice exhibited significantly lower levels of superoxide anion, DNA oxidation marker and NADPH oxidase (Nox) subunits, along with higher expression of antioxidant enzymes. These trends correlated with a reduction in parameters of renal damage (albuminuria, creatinine and tubular injury), atherosclerosis (lesion size) and inflammation (leukocytes and chemokines). Mechanistic studies in renal, vascular and phagocytic cells exposed to cytokines and high-glucose showed that SOCS1 blocked ROS generation by inhibiting both Nox complex assembly and Nox subunit expression, an effect mediated by inactivation of JAK2, STAT1, and PI3K signaling pathways. This study provides evidence for SOCS1-targeted therapies, especially SOCS1 peptidomimetic, as an alternative antioxidant strategy to limit the progression of diabetic micro- and macrovascular complications.The authors investigated the effect of therapies based on the JAK/STAT regulator SOCS1 to combat diabetes-induced oxidative stress. The SOCS1 gene and peptidomimetic administration prevents renal damage and atherosclerosis in streptozotocin-diabetic mice by reducing oxidative stress and enhancing antioxidant genes. Mechanistically, SOCS1 prevents activation/expression of NADPH oxidase via PI3K and STAT1 inhibition.

The use of carbon dioxide angiography for renal sympathetic denervation: a technical report.

Hypertension is the leading attributable cause of cardiovascular mortality worldwide. Patients with hypertension have multiple comorbidities including high rates of concomitant renal disease. Current pharmacological approaches are inadequate in the treatment of resistant hypertension. Renal sympathetic denervation (RDN) has been shown to effectively treat resistant hypertension. The traditional use of iodinated contrast in RDN is contraindicated in patients with significant renal insufficiency. In patients with renal impairment, carbon dioxide (CO2) can be used as an alternative contrast material for RDN. This article describes the technical aspects of RDN using CO2 angiography. Our centre is experienced in the innovative RDN procedure using CO2 angiography. We describe the protocol for CO2 angiography for RDN using a home-made CO2 delivery system and the Symplicity™ (Minneapolis MN 55432 USA) catheter (Medtronic) device. CO2 angiography is an excellent alternative to iodinated contrast for RDN procedures. CO2 angiography for RDN is a safe and effective alternative to iodinated contrast. RDN using CO2 angiography is an easy and feasible procedure that can be used in patients with renal insufficiency or iodinated contrast allergies. Advances in knowledge: There is a paucity of descriptive reports for CO2 angiography for RDN and we provide details of the optimal protocol for the procedure. In particular, we describe the use of a Symplicity Spyral™ catheter (Medtronic), which has not been reported to date for use in this procedure.

Platelet aggregometry cannot identify uremic platelet dysfunction in heart failure patients prior to cardiac surgery.

Patients with heart failure often have concomitant renal disease which can result in uremic platelet dysfunction. Determining whether uremia has affected platelets by platelet aggregometry can be challenging in these patients since they are often on antiplatelet medications. This study was undertaken to determine if platelet aggregation studies could identify heart failure patients at risk for uremic bleeding prior to cardiac surgery. Platelet aggregation studies from three groups were studied and compared: 17 heart failure patients with mild to moderate renal impairment, 17 heart failure patients without renal abnormalities and 17 healthy volunteers. Platelet aggregation was severely impaired in both heart failure groups with and without renal abnormalities compared to healthy controls, and there were no significant differences in platelet aggregation in response to any of the agonists. There was a pan-decrease in platelet aggregation to all agonists in all heart failure patients. Platelet aggregometry does not appear to be useful in measuring platelet dysfunction in heart failure patients with mild to moderate renal impairment.