Higher Risk Of Renal Impairment Research Articles

Feasibility and safety of non-contrast optical coherence tomography imaging using hydroxyethyl starch in coronary arteries

Intracoronary optical coherence tomography (OCT) requires injection of flushing media for image acquisition. Alternative flushing media needs to be investigated to reduce the risk of contrast-induced renal dysfunction. We investigated the feasibility and safety of pentastarch (hydroxyethyl starch) for clinical OCT imaging. We prospectively enrolled 43 patients with 70 coronary lesions (46-stented; 24-native). Total 81 OCT pullback pairs were obtained by manual injection of iodine contrast, followed by pentastarch. Each pullback was assessed frame-by-frame using an automated customized lumen contour/stent strut segmentation algorithm. Paired images were compared for the clear image segments (CIS), blood-flushing capability, and quantitative morphometric measurements. Overall image quality, as assessed by the proportion of CIS, was comparable between the contrast- and pentastarch-flushed images (97.1% vs. 96.5%; p = 0.160). The pixel-based blood-flushing capability was similar between the groups (0.951 [0.947–0.953] vs. 0.950 [0.948–0.952], p = 0.125). Quantitative two- and three-dimensional morphometric measurements of the paired images correlated well (p < 0.001) with excellent inter-measurement variability. All patients safely underwent OCT imaging using pentastarch without resulting in clinically relevant complications or renal deterioration. Non-contrast OCT imaging using pentastarch is clinically safe and technically feasible with excellent image quality and could be a promising alternative strategy for patients at high risk of renal impairment.

Discovering a trans-omics biomarker signature that predisposes high risk diabetic patients to diabetic kidney disease

Diabetic kidney disease is the leading cause of end-stage kidney disease worldwide; however, the integration of high-dimensional trans-omics data to predict this diabetic complication is rare. We develop artificial intelligence (AI)-assisted models using machine learning algorithms to identify a biomarker signature that predisposes high risk patients with diabetes mellitus (DM) to diabetic kidney disease based on clinical information, untargeted metabolomics, targeted lipidomics and genome-wide single nucleotide polymorphism (SNP) datasets. This involves 618 individuals who are split into training and testing cohorts of 557 and 61 subjects, respectively. Three models are developed. In model 1, the top 20 features selected by AI give an accuracy rate of 0.83 and an area under curve (AUC) of 0.89 when differentiating DM and non-DM individuals. In model 2, among DM patients, a biomarker signature of 10 AI-selected features gives an accuracy rate of 0.70 and an AUC of 0.76 when identifying subjects at high risk of renal impairment. In model 3, among non-DM patients, a biomarker signature of 25 AI-selected features gives an accuracy rate of 0.82 and an AUC of 0.76 when pinpointing subjects at high risk of chronic kidney disease. In addition, the performance of the three models is rigorously verified using an independent validation cohort. Intriguingly, analysis of the protein–protein interaction network of the genes containing the identified SNPs (RPTOR, CLPTM1L, ALDH1L1, LY6D, PCDH9, B3GNTL1, CDS1, ADCYAP and FAM53A) reveals that, at the molecular level, there seems to be interconnected factors that have an effect on the progression of renal impairment among DM patients. In conclusion, our findings reveal the potential of employing machine learning algorithms to augment traditional methods and our findings suggest what molecular mechanisms may underlie the complex interaction between DM and chronic kidney disease. Moreover, the development of our AI-assisted models will improve precision when diagnosing renal impairment in predisposed patients, both DM and non-DM. Finally, a large prospective cohort study is needed to validate the clinical utility and mechanistic implications of these biomarker signatures.

Development of minimal resource pre-screening tools for chronic kidney disease in people with type 2 diabetes

Regular chronic kidney disease (CKD) screening can facilitate earlier diagnosis of CKD and preventative action to reduce the risk of CKD progression. People with type 2 diabetes are at a higher risk of developing CKD; hence, it is recommended that they undergo annual screening. However, resources may be limited, particularly in lower-to-middle income countries, and those at the highest risk of having an abnormal CKD screening result should be prioritised for screening. We have developed models to determine which patients are at a high risk of renal impairment. We have shown that, for people with type 2 diabetes and no previous diagnosis of CKD stage 3-5, it is possible to use age, gender, body mass index, duration of type 2 diabetes and blood pressure information to detect those at a higher risk of a reduced glomerular filtration rate. When blood measurements are available, triglyceride and cholesterol measurements can be used to improve the estimate of the risk. Even though risk factors were associated with an increased urine albumin:creatinine ratio, we found no clinical benefit of using the model over a screen-all approach.

Effectiveness and safety of adjunctive inhaled antibiotics for ventilator-associated pneumonia: A systematic review and meta-analysis of randomized controlled trials.

The efficacy and safety of adjunctive inhaled antibiotic therapy for ventilator-associated pneumonia (VAP) was systematically reviewed based on updated studies. We searched four databases and four clinical trial registration platforms to identify relevant studies published prior to May 19, 2020. Randomized controlled trials (RCTs) assessing adjunctive antibiotic inhalation treatment for VAP patients were eligible for this review. Two reviewers independently screened the articles and extracted the data. Information on inhaled therapy and clinical outcomes was collected. Study quality was assessed with the Cochrane risk of bias tool. The meta-analysis was conducted with Review Manager and R software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to evaluate the quality of evidence for each pooled outcome. Eleven RCTs and 1210 patients were included in this analysis after the application of the inclusion and exclusion criteria. Compared with the use of intravenous injection alone, the use of adjunctive inhaled antibiotic therapy improved the rates of clinical cure (relative risk (RR) 1.13, 95% CI [1.02,1.26]) and microbiological eradication (RR 1.45, 95% CI [1.19,1.76]) in VAP patients. However, despite these improvements, mortality was not reduced (RR 1.00, 95% CI [0.82,1.21]). Adjunctive antibiotics delivered through the respiratory tract were not associated with a higher risk of renal impairment but were associated with an increased risk of bronchospasm (RR 2.74, 95% CI [1.31,5.73] during treatment. Adjunctive inhaled antibiotics improved the clinical outcomes in VAP patients, but the increased rates clinical cure and microbiological eradication were not associated with reduced mortality. The use of nebulized antibiotics is not supported by the currently available evidence as a routine therapeutic strategy for VAP. CRD42020186970.

Renal impairment in a large-scale HIV preexposure prophylaxis implementation cohort.

HIV preexposure prophylaxis (PrEP) with fixed-dose tenofovir disoproxil fumarate (TDF) and emtricitabine has been associated with low rates of renal impairment in clinical trials. Large-scale PrEP implementation may result in higher rates, as the prevalence of associated risk factors may be higher than in trial populations. A posthoc analysis of EPIC-NSW, a large Australian multicentre PrEP implementation trial for patients at high risk of HIV infection. Participants were eligible for inclusion if they commenced PrEP between 1 March 2016 and 30 April 2018, and had renal function assessed at baseline and at least once more before the censor date. The primary outcome was new-onset renal impairment, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2. A total of 6808 participants were eligible for inclusion. Almost all were male (99%), with a median age of 35 years [interquartile range (IQR): 28-44]. Approximately one-quarter (26%) had a baseline eGFR <90 ml/min per 1.73 m2. Over a median follow-up period of 1.2 years (IQR: 0.6-1.7), the rate of renal impairment was 5.8 episodes per 1000 person-years [95% confidence interval (CI): 4.0-7.8]. In multivariable Cox regression, there was a higher risk of renal impairment in participants aged ≥50 years [hazard ratio (HR) 14.7, 95% CI: 5.0-43.3, P < 0.001] and those with an eGFR <90 ml/min per 1.73 m2 (HR 28.9, 95% CI: 6.9-121.9) at baseline. In a large-scale implementation study, TDF-containing PrEP was associated with a low risk of renal impairment overall, whereas older patients and those with preexisting renal dysfunction were at substantially increased risk.

Association between neutrophils and renal impairment of rheumatoid arthritis: A retrospective cross-sectional study.

ObjectivePrevious studies have shown that increased neutrophils, as a manifestation of oxidative stress, may be involved in the progression of kidney disease. To our knowledge, little is known about the relationship between neutrophils and renal impairment in rheumatoid arthritis (RA). Therefore, we aim to investigate whether neutrophil is associated with renal impairment in RA patients.MethodsWe retrospectively investigated the renal function of 602 RA patients in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine by estimated glomerular filtration rate (eGFR) from September 2018 and September 2019. The exposure variable was neutrophils, and the main outcome was eGFR. General data (gender, age, duration, hypertension, diabetes, hobbies, and medication history), whole blood markers, lipid indexes, and inflammatory indexes were collected as much as possible. We used multivariable logistic regression analysis to evaluate the association between neutrophils and renal impairment in RA participants.ResultsA total of 89 cases (14.8%) had renal impairment with eGFR < 60 ml/min/1.73 m2, and 75 cases (84.3%) were female. Subgroup analysis showed that female (odds ratio [OR] = 0.523, 95% confidence interval [CI]: 0.318–0.867, p = .011), neutrophils greater thsn 7.5 × 109/L (OR = 2.314, 95% CI: 1.310–4.087, p = .004), NLR > 3.53 (OR = 1.757, 95% CI: 1.104–2.799, p = .018), hemoglobin less than 120 g/L (OR = 2.413, 95% CI: 1.418–4.118, p = .001), and UA > 360 μmol/L (OR = 6.052, 95% CI: 3.708–9.878, p < .001) was related to renal damage in RA. Adjusted for several confounders, the multivariable analysis indicated that neutrophils greater than 7.5 × 109/L (OR = 1.784, 95% CI: 1.164–3.288, p = .031) was independently associated with an increased risk of renal impairment in RA.ConclusionOur study demonstrated that neutrophils greater than 7.5 × 109/L was associated with a high risk of renal impairment in RA, suggesting that neutrophil may be a biomarker for renal impairment in RA.

Acute Renal Problems Still a Great Challenge in Obstetrics

Objective: To assess the early risk factors and outcomes of the patients presented with acute renal issues, at tertiary care Hospital.&#x0D; Methodology: This descriptive study was conducted at gynaecology and obstetrics department of Liaquat University of medical and health Sciences. Study duration was six months from June 2019 to November 2019. Women having age more than 18 years, developed renal impairment as serum creatinine level more than 1.2 mg/dl were included. All data was collected via self-made proforma. SPSS version 20 was used for the data analysis.&#x0D; Results: Total 58 women having renal problems during pregnancy were studied, their mean age was 28.40+4.68 years and mean gestational age was 28.40+4.68 years. Most of the women 70.2% were un-booked. Parity 1-3 was commonest. Anaemic women were on high risk of renal impairment as most of the patients had moderate anemia. Hypertension was in 35.1% patients, placental abruption was in 10.5% cases, tow patients had diabetes, 12.3% presented with pregnancy induced hypertension and postpartum haemorrhage was in 05.3% cases. There was a significant negative correlation between haemoglobin level and serum creatinine level, (r-value 0.029).&#x0D; Conclusion: Anemia was the commonest reason for renal impairment during pregnancy. Most of the women were un-booked, having high parity and were presented with anemia. This morbidity can be decreased and prevented by stabilizing the haemoglobin level by taking proper antenatal care.

Association between atherogenic index of plasma and renal function impairment in patients with gout

Objective To study the relationship between atherogenic index of plasma (AIP)and renal impairment in male patients with gout. Methods A retrospective analysis of 821 male subjects was conducted to measure the relevant biochemical indicators and to calculate the AIP, endogenous creatinine-clearance rate (Ccr), and estimated glomerular filtration rate (eGFR). EpiData 3.1 software was used for data entry, SPSS21.0 was used for statistical analysis, and GraphPad Prism 6.0 software was used for charts. Results Compared with control group, AIP, serum uric acid, triglyceride in gout group were significantly higher (all P 0.05), while Ccr and serum uric acid levels gradually increased (P<0.05). Logistic regression analysis after adjusting for various confounding factors showed that AIP, triglyceride, and serum uric acid were risk factors for renal function damage in patients with gout (P<0.05), the relevant risk were 7.030, 1.291, 1.004 respectively. After adjusting confounding factors, the associations between triglyceride, serum uric acid and renal function injury risk changed little, while AIP showed more evident, the OR value increased from 2.629 to 6.265 and 7.030. Conclusions (1)AIP is closely related to the renal function damage of patients with gout. After adjusting various confounding factors, AIP can better reflect the renal function damage than other indicators, which is of great significance to predict the renal function damage of patients with gout. (2)That patients with gout with high uric acid level may suffer from renal atherosclerosis and have a higher risk of renal impairment. (3)Dynamic observation of AIP in gout patients is helpful for early identification of the risk of renal failure in such patients. Key words: Gout; Renal damage; Atherogenic index of plasma; Confounding factors

The value of symmetrical ambulatory arterial stiffness index should be noted in prediction of early renal impairment in patients with essential hypertension

Objective To investigate the predictive value of symmetrical ambulatory arterial stiffness index (S-AASI) in detecting early renal impairment of patients with essential hypertension. Methods Totally 245 consecutive out-patients were confirmed with essential hypertension, and were divided into group A (56 cases), group B (64 cases), group C (72 cases), and group D (53 cases) according to the quartile of S-AASI. The combination testing of serum cystatin C, serum β2-microglobulin as well as urine microalbumin to creatinine ratio were implemented as laboratory diagnosis index of renal impairment in early stage and 109 essential hypertension patients were diagnosed with early renal impairment. The parameters were compared among 4 groups. Pearson correlation analysis and partial correlation analysis were performed to confirm the relationship between the markers of early renal impairment and S-AASI. The predictive value of S-AASI to detect early renal injury was evaluated by analyzing Receiver Operating Characteristic (ROC) curve. Results With the rising of S-AASI, age as well as 24 hours mean systolic blood pressure (24 h SBP), serum cystatin C, serum β2-microglobulin, urine microalbumin to creatinine ratio and the incidence rate of early renal injury went notably higher while estimated glomerular filtration rate (eGFR) decreased significantly. After controlling for age, correlation test showed S-AASI was positively correlated with24hSBP, serum cystatin C, serumβ2-microglobulin, urine microalbumin to creatinine ratio(r=0.392, 0.627, 0.514 and 0.643 respectively, P<0.05)and negatively correlated with eGFR(r=-0.312, P<0.05). The 24 hours mean diastolic blood pressure (24 h DBP) was uncorrelated with S-AASI. Area under ROC curve of S-AASI for diagnosis of hypertensive renal impairment was 0.885. The critical value of S-AASI was 0.17, the sensitivity, specificity, positive predictive value, and negative predictive value were 92.7%, 65.2%, 68.5%, and 91.7%, respectively. Conclusions When S-AASI was detected above 0.17, patients with hypertension had a higher risk of renal impairment. Higher S-AASI was correlated with worse early renal impairment laboratory indexes. The predictive accuracy of S-AASI for early hypertensive renal impairment was medium. Key words: Arteriosclerosis; Hypertension/CO; Kidney diseases/CO; Forecasting

Renal Perfusion and Function during Pneumoperitoneum: A Systematic Review and Meta-Analysis of Animal Studies.

Both preclinical and clinical studies indicate that raised intra-abdominal pressure (IAP) associated with pneumoperitoneum during laparoscopic surgical procedures can cause renal damage, the severity of which may be influenced by variables such as pressure level and duration. Several of these variables have been investigated in animal studies, but synthesis of all preclinical data has not been performed. This systematic review summarizes all available pre-clinical evidence on this topic, including an assessment of its quality and risk of bias. We performed meta-analysis to assess which aspects of the pneumoperitoneum determine the severity of its adverse effects. A systematic search in two databases identified 55 studies on the effect of pneumoperitoneum on renal function which met our inclusion criteria. There was high heterogeneity between the studies regarding study design, species, sex, pressure and duration of pneumoperitoneum, and type of gas used. Measures to reduce bias were poorly reported, leading to an unclear risk of bias in the majority of studies. Details on randomisation, blinding and a sample size calculation were not reported in ≥80% of the studies. Meta-analysis showed an overall increase in serum creatinine during pneumoperitoneum, and a decrease in urine output and renal blood flow. Subgroup analysis indicated that for serum creatinine, this effect differed between species. Subgroup analysis of pressure level indicated that urine output decreased as IAP level increased. No differences between types of gas were observed. Data were insufficient to reliably assess whether sex or IAP duration modulate the effect of pneumoperitoneum. Four studies assessing long-term effects indicated that serum creatinine normalized ≥24 hours after desufflation of pneumoperitoneum at 15mmHg. We conclude that harmful effects on renal function and perfusion during pneumoperitoneum appear to be robust, but evidence on long-term effects is very limited. The reliability and clinical relevance of these findings for healthy patients and patients at high risk of renal impairment remain uncertain. We emphasize the need for rigorous reporting of preclinical research methodology, which is of vital importance for clinical translation of preclinical data.

Telbivudine Protects Against Renal Impairment in Patients With Chronic Hepatitis B Infection

It has been reported that treatment with telbivudine might be associated with a significant improvement of renal function in patients with chronic hepatitis B. To confirm this finding, a systematic literature review was conducted. Four online databases (PubMed, CNKI/FMJS, Ovid and SpringerLink) were searched. Serum creatinine, glomerular filtration rate and estimated glomerular filtration rate changes from baseline to the end of the treatment were analyzed. A total of seven full-text articles and 13 abstracts with sample sizes ranging from 15 to 689 patients fulfilled the selection criteria for review. The results showed that long-term treatment with telbivudine, either as monotherapy or combined with other nucleos(t)ide analogs, can significantly improve renal function in chronic hepatitis B patients, particularly those at high risk of renal impairment.

Optimizing the Clinical Use of Vancomycin.

The increasing number of infections produced by beta-lactam-resistant Gram-positive bacteria and the morbidity secondary to these infections make it necessary to optimize the use of vancomycin. In 2009, the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Disease Pharmacists published specific guidelines about vancomycin dosage and monitoring. However, these guidelines have not been updated in the past 6 years. This review analyzes the new available information about vancomycin published in recent years regarding pharmacokinetics and pharmacodynamics, serum concentration monitoring, and optimal vancomycin dosing in special situations (obese people, burn patients, renal replacement therapy, among others). Vancomycin efficacy is linked to a correct dosage which should aim to reach an area under the curve (AUC)/MIC ratio of ≥400; serum trough levels of 15 to 20 mg/liter are considered a surrogate marker of an AUC/MIC ratio of ≥400 for a MIC of ≤1 mg/liter. For Staphylococcus aureus strains presenting with a MIC >1 mg/liter, an alternative agent should be considered. Vancomycin doses must be adjusted according to body weight and the plasma trough levels of the drug. Nephrotoxicity has been associated with target vancomycin trough levels above 15 mg/liter. Continuous infusion is an option, especially for patients at high risk of renal impairment or unstable vancomycin clearance. In such cases, vancomycin plasma steady-state level and creatinine monitoring are strongly indicated.

PP.36.07

Objective: To assess influence of antecedent hypertension on clinical course, cardiac hemodynamics and renal function in patients with acute decompensated heart failure (ADHF). Design and method: We performed a prospective observational study of patients admitted in cardiology ICU with ADHF. A total of 58 patients were enrolled including 40 men (69,0%) and 18 women (31,0%), mean age 64,2 ± 2,3 years. Patients were divided into 2 groups, gr.1 - n = 41 (70,7%) with antecedent hypertension and gr.2 - n = 17 (29,3%) without hypertension. The degree of kidney impairment was assessed by estimation of glomerular filtration rate (eGFR), plasma NT-pro-BNP (ELISA) was measured at the day of admission. Results: There was no significant difference between gr.1 and gr.2 for a frequency of diabetes mellitus 27 (65,9%) vs 10 (58,8%) and atrial fibrillation 15 (36,6%) vs 6 (35,3%), (all p > 0,05). In hypertensive patients renal damage (eGFR < 60 ml/min) was more frequent - 24 (58,5%) vs 5 (29,4%), (p < 0,05). Also patients in gr.1 had higher ejection fraction - 42,7 ± 2,2% vs 38,1 ± 2,1% (p < 0,05), had longer duration of stay in hospital 12,3 ± 2,1 vs 9,1 ± 1,9 days, (p < 0,05). NT-pro-BNP at the 1-st day was significantly higher in gr.1 comparing to gr.2 - 1108 ± 317 vs 837 ± 284 pg/ml, (p < 0,02). Conclusions: In patients admitted in cardiology ICU with ADHF, preexisting hypertension is associated with higher risk of renal impairment, longer duration of stay, and higher NT-pro-BNP.

Antihypertensive Drugs, Hypotension, and Ischemic Colitis

In this issue of the journal, Hines et al. [1] report incidence rates of ischemic colitis in treated hypertensive adults in the USA, with a focus on aliskiren, a direct renin inhibitor. While these investigators are to be commended for assessing such a large dataset (2,356,226 hypertensive patients), they provide no clear explanation for the focus on aliskiren. The ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) trial, which concerned patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, was stopped prematurely because of a slight excess risk of cardiovascular events in patients receiving aliskiren plus an angiotensin receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) compared with those receiving placebo plus an ARB or ACEI. This study also demonstrated a significantly higher risk of renal impairment, hypotension, and hyperkalemia in the aliskiren group [2]. Consequently, the US FDA modified the labeling of aliskiren in April 2012 with a new contraindication against the use of aliskiren with ARBs or ACEIs in patients with diabetes, and a warning to avoid the use of aliskiren with ARBs or ACEIs in patients with moderate to severe renal impairment [3] The European Medicines Agency (EMA) contraindicated aliskiren in both situations [4]. One and a half years later, the FDA published a new warning and precaution about symptomatic hypotension that may occur after initiation of aliskiren in patients with marked volume depletion, those with salt depletion, or those receiving other agents acting on the renin–angiotensin–aldosterone system [5]. More recently, in light of two other clinical trials and a meta-analysis [6–8], the EMA recommended against the prescription of dual reninangiotensin system blockade through the combined use of ACEIs, ARBs, or aliskiren [9] because these combinations were associated with an increased risk of hyperkalemia, kidney damage, and hypotension. Furthermore, no significant benefits from dual blockade were seen in patients without heart failure. Benefits were thought to outweigh risks only in a selected group of patients with heart failure in whom other treatments were unsuitable. Hypotension is a risk factor of ischemic colitis, an uncommon, potentially severe, and sometimes fatal disease caused by a lack of blood flow. It is also a diagnosis of exclusion with no identified cause [10, 11]. The ageand sex-adjusted incidence rate was estimated to be 22.9 per 100,000 patient-years (PYs) (95 % confidence interval [CI] 18.6–27.3) for the period 2006–2009 among unselected subjects in a US county [12]. The incidence was twice as frequent for women and increased strongly with age, from 1.1 per 100,000 PYs before the age of 40 years to 107 per 100,000 PYs for subjects aged 80 years or older [10]. In this study, the main risk factor was a hypotensive episode in the previous month (odds ratio [OR] 33.0, 95 % CI 13.3–80.9) [11]. Other independent risk factors identified were collagen vascular disease (OR 8.0, 95 % CI 2.2–28.3), peripheral vascular disease (OR 7.9, 95 % CI 4.7–13.2), congestive heart failure (OR 4.1, 95 % CI 2.6–6.3), psychotropic medications used in the past This comment refers to the article available at doi:10.1007/s40256-014-0101-4.

Pharmacodynamics, Efficacy and Safety of Sodium–Glucose Co-Transporter Type 2 (SGLT2) Inhibitors for the Treatment of Type 2 Diabetes Mellitus

Inhibitors of sodium-glucose co-transporter type 2 (SGLT2) are proposed as a novel approach for the management of type 2 diabetes mellitus (T2DM). Several compounds are already available in many countries (dapagliflozin, canagliflozin, empagliflozin and ipragliflozin) and some others are in a late phase of development. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with a rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug. SGLT2 co-transporters are responsible for reabsorption of most (90%) of the glucose filtered by the kidneys. The pharmacological inhibition of SGLT2 co-transporters reduces hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycaemia and the glomerular filtration rate. Results of numerous placebo-controlled randomised clinical trials of 12-104weeks duration have shown significant reductions in glycated haemoglobin (HbA1c), resulting in a significant increase in the proportion of patients reaching HbA1c targets, and a significant lowering of fasting plasma glucose when SGLT2 inhibitors were administered as monotherapy or in addition to other glucose-lowering therapies including insulin in patients with T2DM. In head-to-head trials of up to 2years, SGLT2 inhibitors exerted similar glucose-lowering activity to metformin, sulphonylureas or sitagliptin. The durability of the glucose-lowering effect of SGLT2 inhibitors appears to be better; however, this remains to be more extensively investigated. The risk of hypoglycaemia was much lower with SGLT2 inhibitors than with sulphonylureas and was similarly low as that reported with metformin, pioglitazone or sitagliptin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Both effects were very consistent across the trials and they represent some advantages for SGLT2 inhibitors when compared with other oral glucose-lowering agents. The pharmacodynamic response to SGLT2 inhibitors declines with increasing severity of renal impairment, and prescribing information for each SGLT2 inhibitor should be consulted regarding dosage adjustments or restrictions in moderate to severe renal dysfunction. Caution is also recommended in the elderly population because of a higher risk of renal impairment, orthostatic hypotension and dehydration, even if the absence of hypoglycaemia represents an obvious advantage in this population. The overall effect of SGLT2 inhibitors on the risk of cardiovascular disease is unknown and will be evaluated in several ongoing prospective placebo-controlled trials with cardiovascular outcomes. The impact of SGLT2 inhibitors on renal function and their potential to influence the course of diabetic nephropathy also deserve more attention. SGLT2 inhibitors are generally well-tolerated. The most frequently reported adverse events are female genital mycotic infections, while urinary tract infections are less commonly observed and generally benign. In conclusion, with their unique mechanism of action that is independent of insulin secretion and action, SGLT2 inhibitors are a useful addition to the therapeutic options available for the management of T2DM at any stage in the natural history of the disease. Although SGLT2 inhibitors have already been extensively investigated, further studies should even better delineate the best place of these new glucose-lowering agents in the already rich armamentarium for the management of T2DM.

Higher risk of renal impairment associated with tenofovir use amongst people living with HIV in India: A comparative cohort analysis between Western India and United Kingdom

BackgroundData on the renal safety of Tenofovir (TDF) in Low and Middle Income Countries (LMICs) is scarce. We compared development of various forms of renal impairment with use of TDF-containing antiretroviral therapy (ART) between a cohort from the Institute of Infectious Diseases (IID) Pune, Western India and the Royal Free Hospital (RFH) London, UK.MethodsThis is a retrospective analysis of change in estimated glomerular filtration rates (eGFRs) at 6, 12 and 24 months post TDF initiation using the Modification of Diet in Renal Disease (MDRD) equation. In people living with Human Immunodeficiency virus (PLHIV) with pre-TDF eGFR > 90 ml/min/1.73 m2 time to development of and factors associated with progression to eGFR < 60 ml/min/1.73 m2 were calculated using standard survival methods.ResultsA total of 574 (59% Caucasian) at the RFH, and 708 (100% Indian ethnicity) PLHIV from IID were included. Baseline median eGFR were similar; RFH 102 (IQR 89, 117), IID 100 (82, 119). At 24 months, mean (SD) decline in eGFR was -7(21) at RFH (p < 0.0001) and -7(40) at IID (p = 0.001). Amongst those with pre-TDF eGFR > 90 ml/min/1.73 m2 PLHIV at IID were more likely to develop an eGFR < 60 ml/min/1.73 m2 (aHR = 7.6 [95% CI 3.4, 17.4] p < 0.0001) and had a faster rate of progression estimated using Kaplan Meier methods. Risk factors included age (per 10 years older: aHR = 2.21 [1.6, 3.0] p < 0.0001) and receiving concomitant ritonavir boosted Protease Inhibitor (PI/r) (aHR = 2.4 [1.2, 4.8] p = 0.01).ConclusionsThere is higher frequency of treatment limiting renal impairment events amongst PLHIV receiving TDF in Western India. As TDF scale up progresses, programs need to develop capacity for monitoring and treatment of renal impairment associated with TDF.

U-shaped association between central body fat and the urinary albumin-to-creatinine ratio and microalbuminuria

BackgroundThe prevalence of obese and overweight patients has increased dramatically worldwide. Both are common risk factors for chronic kidney disease (CKD) as indicated by a diminished estimated glomerular filtration rate (eGFR) or microalbuminuria. This study aimed to investigate whether anthropometric parameters [waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI)] are associated with renal function in a population-based study of Caucasian subjects.MethodsData from 3749 subjects (1825 women) aged 20 to 81 years from the Study of Health in Pomerania (SHIP) were analysed. Renal indices, including the urinary albumin-to-creatinine ratio (uACR), microalbuminuria, eGFR and CKD, were studied. Parameters of anthropometry (WC, WHtR and BMI) were categorised into sex-specific quintiles.ResultsAnalysis of variance (ANOVA) models, adjusting for age, sex, type 2 diabetes mellitus and hypertension, revealed that a high and low WC or WHtR and low BMI were independently related to a higher uACR. Logistic regression models confirmed these results with respect to uACR and showed that subjects with a high or low WC or a high WHtR had increased odds of microalbuminuria. The ANOVA models revealed no relations of the investigated anthropometric parameters with eGFR. However, subjects with high values for these parameters had increased odds of CKD.ConclusionsOur results demonstrate U-shaped associations between markers of central fat distribution and uACR or microalbuminuria in the general population, suggesting that both obese and very thin subjects have a higher risk of renal impairment.

Renal toxicity in patients with multiple myeloma receiving zoledronic acid vs. ibandronate: A retrospective medical records review

This retrospective study investigated the rates of renal impairment in patients with multiple myeloma treated with zoledronic acid and ibandronate. We retrospectively reviewed medical records in a German oncology clinic, from May 2001 to December 2005. Creatinine measurements were analyzed from baseline (before zoledronic acid or ibandronate treatment) to last evaluation for each patient. A total of 84 patients were included. Zoledronic acid increased the risk of renal impairment by approximately 3-fold compared with ibandronate (renal impairment rates: zoledronic acid 37.7% vs. ibandronate 10.5%, relative risk [RR]=3.6, P=0.0029 serum creatinine [SCr]; 62.3% vs. 23.7%, RR=2.6, P=0.0001 glomerular filtration rate [GFR]). Ibandronate-treated patients switched from zoledronic acid had a significantly higher risk of renal impairment than patients receiving ibandronate monotherapy (zoledronic acid over ibandronate 39.1% vs. ibandronate monotherapy 6.7%, RR= 5.9, P=0.028 [SCr]; 65.2% vs 26.7%, RR=2.4, P=0.022 [GFR]). Multivariate analysis found significantly higher hazard ratios for zoledronic acid over ibandronate (SCr: Cox = 4.38, P=0.01; Andersen-Gill=8.22, P < 0.01; GFR: Cox = 4.31, P < 0.01; Andersen-Gill = 3.71, P < 0.01). Overall, this retrospective study suggests that multiple myeloma patients are more likely to experience renal impairment with zoledronic acid than with ibandronate. The risk of renal impairment increased if patients had received prior therapy with zoledronic acid.

High risk of renal impairment during long-term adefovir and lamivudine combination therapy in patients with lamivudine-resistant chronic hepatitis B

High risk of renal impairment during long-term adefovir and lamivudine combination therapy in patients with lamivudine-resistant chronic hepatitis B

Renal toxicity associated with zoledronic acid and pamidronate in multiple myeloma patients: A retrospective study

17515 Background: Patients (pts) with multiple myeloma (MM) are at an increased risk of renal impairment as part of disease progression. Herein we compared rates of renal toxicity in MM pts treated with zoledronic acid (ZO), pamidronate (PA), and no bisphosphonate (BP) treatment (NT). Methods: Medical and pharmacy claims and laboratory data were reviewed from &gt;35 managed care plans between 01/2000 and 12/2004. Inclusion criteria were ≥2 claims for MM, no gap in health coverage, and serum creatinine readings before and after first ZO or PA infusion. MM pts who received NT served as a separate reference group. Observation periods extended from initial BP infusion to health plan disenrollment (BP monotherapy) or BP switch. Renal impairment was defined as a ≥25% decrease in glomerular filtration rate (GFR,abbreviated MDRD formula) from baseline. Andersen-Gill model, adjusted for demographics and baseline comorbidities, was used to analyze multiple events in a given pt, as physician practice patterns indicate that administration of both BPs continues even after the development of a first renal event. Results: The study population comprised 122 ZO-treated pts, 90 PA-treated pts, and 213 NT pts. Baseline characteristics of ZO and PA groups were similar except the ZO group had a significantly better baseline GFR and higher previous nephrotoxic drug use (both p &lt; 0.01). After treatment, ZO and PA groups had similar renal impairment rates that were significantly higher than the NT group and increased with treatment duration (ZO 21.7%, PA 22.9%, NT 17.0% in pts treated for &lt;6 months; increasing to ZO 53.8%, PA 50.0%, NT 33.7% in pts treated for ≥18 months). Mean renal impairment events per person-year were significantly higher for ZO than PA (1.83 vs 0.78, p &lt; 0.001). Multiple-event analysis found a 2.6 times risk of renal impairment for ZO than PA (p &lt; 0.0001). Compared with PA, ZO-treated pts had a steeper decrease in mean GFR from baseline by 8.5% (p = 0.03). Conclusions: This retrospective observational study suggests that in MM patients, both ZO and PA are associated with a similar higher risk of renal impairment than NT, but ZO-treated pts are significantly more likely to experience multiple impairment events upon repeated administrations. [Table: see text]