Development Of Impaired Renal Function Research Articles

Renal outcomes of early rhythm control in patients with atrial fibrillation and chronic kidney disease

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): The Patient-Centered Clinical Research Coordinating Center (PACEN) funded by the Ministry of Health & Welfare, Republic of Korea Background Atrial fibrillation (AF) is associated with development of impaired renal function and chronic kidney disease (CKD). Early rhythm control initiated within 1 year of AF diagnosis is associated with a lower risk of adverse cardiovascular outcomes compared to usual care among patients recently diagnosed with AF. Purpose This study aimed to assess the effects of early rhythm control on renal function in patients with AF and CKD, compared with rate control Methods This population-based cohort study included 4,151 patients with AF and CKD, from the Korean National Health Insurance Service database, undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis in 2005–2015. A composite renal outcome of ≥30% decline in estimated glomerular filtration rate (eGFR), acute kidney injury (AKI), and kidney failure was compared using propensity score overlap weighting. Results In the study population (39.1% female; median age: 70 years), a total of 628 composite renal outcome occurred during the median follow-up of 2.3 years. Early rhythm control, compared with rate control, was associated with lower risks of the composite renal outcome (weighted incidence rate: 4.1 vs. 5.3 per 100 person-years; weighted HR 0.78, 95% CI 0.65-0.94) and kidney failure (weighted HR 0.73, 95% CI 0.56-0.95). Trends toward lower risks of eGFR decline (weighted HR 0.89, 95% CI 0.58-1.37) and AKI (weighted HR 0.88, 95% CI 0.66-1.17) were observed in patients undergoing early rhythm control, compared with those undergoing rate control. Conclusion Among patients with AF and CKD, early rhythm control was associated with a lower risk of progression of kidney disease, compared with rate control, highlighting the need for future randomized studies evaluating the benefits of early rhythm control on renal outcome among patients with AF.

Heterogeneity in the association between prediabetes categories and reduction on glomerular filtration rate in a 5-year follow-up

Prediabetes and not just diabetes can cause kidney damage. This study assess the association of prediabetes with development of impaired renal function (IRF). We used data from PREDAPS prospective study a cohort of 1072 subjects with prediabetes and another cohort of 772 subjects without prediabetes were follow-up from 2012 to 2017. Prediabetes was defined according to American Association of Diabetes criteria. IRF was defined as having a glomerular filtration rate < 60 mL/min/1.73 m2. Incidence rates of IRF in both cohorts and in different categories of prediabetes, based on impaired glycosylated hemoglobin (HbA1c) and/or fasting plasma glucose (FPG), were calculated. Hazard ratios (HR) for the association of the prediabetes with IRF, adjusting for potential confounders, were estimated by Cox regression models. Incidence rates of IRF per 100 person-years were 1.72 (95% confidence interval [CI]: 1.34–2.21) and 1.79 (95%CI: 1.45–2.20) for those without and with prediabetes, respectively .The HR of IRF in subjects with prediabetes with respect to subjects without prediabetes was 0.76 (95% CI: 0. 54–1.07). Corresponding HRs for type of prediabetes was 0.68 (95%CI: 0.40–1.15) for those with both altered parameters, 0.68 (95%CI: 00.40–1.15) for those with only impaired HbA1c and 1.12 (95%CI: 0.68–1.85) for those with only impaired FPG. The present study reflects an overall trend towards a slightly decreased risk of IRF onset associated to prediabetes except for individuals with only isolated impaired FPG. Further studies are warranted to fully assess the renal progression of each group.

Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial

Microalbuminuria is an early sign of kidney disease in people with diabetes and indicates increased risk of cardiovascular disease. We tested whether a urinary proteomic risk classifier (CKD273) score was associated with development of microalbuminuria and whether progression to microalbuminuria could be prevented with the mineralocorticoid receptor antagonist spironolactone. In this multicentre, prospective, observational study with embedded randomised controlled trial (PRIORITY), we recruited people with type 2 diabetes, normal urinary albumin excretion, and preserved renal function from 15 specialist centres in ten European countries. All participants (observational cohort) were tested with the CKD273 classifier and classified as high risk (CKD273 classifier score >0·154) or low risk (≤0·154). Participants who were classified as high risk were entered into a randomised controlled trial and randomly assigned (1:1), by use of an interactive web-response system, to receive spironolactone 25 mg once daily or matched placebo (trial cohort). The primary endpoint was development of confirmed microalbuminuria in all individuals with available data (observational cohort). Secondary endpoints included reduction in incidence of microalbuminuria with spironolactone (trial cohort, intention-to-treat population) and association between CKD273 risk score and measures of impaired renal function based on estimated glomerular filtration rate (eGFR; observational cohort). Adverse events (particularly gynaecomastia and hyperkalaemia) and serious adverse events were recorded for the intention-to-treat population (trial cohort). This study is registered with the EU Clinical Trials Register (EudraCT 20120-004523-4) and ClinicalTrials.gov (NCT02040441) and is completed. Between March 25, 2014, and Sept 30, 2018, we enrolled and followed-up 1775 participants (observational cohort), 1559 (88%) of 1775 participants had a low-risk urinary proteomic pattern and 216 (12%) had a high-risk pattern, of whom 209 were included in the trial cohort and assigned to spironolactone (n=102) or placebo (n=107). The overall median follow-up time was 2·51 years (IQR 2·0-3·0). Progression to microalbuminuria was seen in 61 (28%) of 216 high-risk participants and 139 (9%) of 1559 low-risk participants (hazard ratio [HR] 2·48, 95% CI 1·80-3·42; p<0·0001, after adjustment for baseline variables of age, sex, HbA1c, systolic blood pressure, retinopathy, urine albumin-to-creatinine ratio [UACR], and eGFR). Development of impaired renal function (eGFR <60 mL/min per 1·73 m2) was seen in 48 (26%) of 184 high-risk participants and 119 (8%) of 1423 low-risk participants (HR 3·50; 95% CI 2·50-4·90, after adjustment for baseline variables). A 30% decrease in eGFR from baseline (post-hoc endpoint) was seen in 42 (19%) of 216 high-risk participants and 62 (4%) of 1559 low-risk participants (HR 5·15, 95% CI 3·41-7·76; p<0·0001, after adjustment for basline eGFR and UACR). In the intention-to-treat trial cohort, development of microalbuminuria was seen in 35 (33%) of 107 in the placebo group and 26 (25%) of 102 in the spironolactone group (HR 0·81, 95% CI 0·49-1·34; p=0·41). In the safety analysis (intention-to-treat trial cohort), events of plasma potassium concentrations of more than 5·5 mmol/L were seen in 13 (13%) of 102 participants in the spironolactone group and four (4%) of 107 participants in the placebo group, and gynaecomastia was seen in three (3%) participants in the spironolactone group and none in the placebo group. One patient died in the placebo group due to a cardiac event (considered possibly related to study drug) and one patient died in the spironolactone group due to cancer, deemed unrelated to study drug. In people with type 2 diabetes and normoalbuminuria, a high-risk score from the urinary proteomic classifier CKD273 was associated with an increased risk of progression to microalbuminuria over a median of 2·5 years, independent of clinical characteristics. However, spironolactone did not prevent progression to microalbuminuria in high-risk patients. European Union Seventh Framework Programme.

The magnitude of obesity and metabolic syndrome among diabetic chronic kidney disease population: A nationwide study.

BackgroundAlthough the prevalence of obesity and metabolic syndrome (MetS) among dialysis patients has been exceeding than general population, little is known regarding obesity and MetS in non-dialysis chronic kidney disease (CKD). We aimed to find the magnitude of obesity and MetS and their associations with impaired renal function among type 2 diabetes mellitus (T2DM) patients.MethodsA national survey of T2DM patients was collected in the Thai National Health Security Office database during 2014–5. The sampling frame was designated as distinct geographic regions throughout the country. A stratified two-stage cluster sampling was used to select the study population. Anthropometry and 12-hour fasting blood samples were obtained by trained personnel. BMI of ≥25 kg/m2 was classified as obesity. MetS was defined as having elevated waist circumference (>90 and >80 cm in men and women, respectively) plus any two of the followings: triglyceride ≥150 mg/dL, HDL-C <40 in men or <50 mg/dL in women, blood pressure ≥130/85 mmHg, and fasting blood sugar ≥100 mg/dL. CKD was defined as an impaired renal function (eGFR <60 mL/min/1.73m2 according to the CKD-EPI equation). Logistic regression analysis was performed to examine the relationship between obesity and MetS with the presence of CKD.ResultsA total of 32,616 diabetic patients were finally recruited from 997 hospitals. The mean age was 61.5±10.9 years with 67.5% women. Of the participants, 35.4% were CKD patients. The prevalence of obesity was 46.5% in CKD and 54.1% in non-CKD patients with T2DM (p<0.001). In contrast, the prevalence of MetS in CKD patients was higher than their non-CKD counterparts (71.3 vs 68.8%, p<0.001). Moreover, there was an association between the prevalence of MetS with CKD stage from 3a to 5 (70.1, 72.3, 73.4, and 72.7%, respectively, p trend = 0.02). MetS, but not obesity, had a significant association with CKD in T2DM patients after adjusting for age, sex, and comorbidities [OR 1.14; 95% CI 1.06–1.22, p<0.001]. When stratified by each component of MetS, only high serum triglyceride and low HDL-C levels were increased in patients with CKD stage 4 and 5 compared with CKD stage 3 (p<0.001) and had a significant relationship with impaired renal function.ConclusionThere were relatively high prevalences of both obesity and MetS in T2DM patients. A higher prevalence of MetS, but lower prevalence of obesity, was observed among diabetic CKD group compared with their non-CKD counterparts. MetS, as a surrogate of insulin resistance, appeared to be more important than obesity in the development of impaired renal function in diabetic population.

Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial

The effect of the α-glucosidase inhibitor acarbose on cardiovascular outcomes in patients with coronary heart disease and impaired glucose tolerance is unknown. We aimed to assess whether acarbose could reduce the frequency of cardiovascular events in Chinese patients with established coronary heart disease and impaired glucose tolerance, and whether the incidence of type 2 diabetes could be reduced. The Acarbose Cardiovascular Evaluation (ACE) trial was a randomised, double-blind, placebo-controlled, phase 4 trial, with patients recruited from 176 hospital outpatient clinics in China. Chinese patients with coronary heart disease and impaired glucose tolerance were randomly assigned (1:1), in blocks by site, by a centralised computer system to receive oral acarbose (50 mg three times a day) or matched placebo, which was added to standardised cardiovascular secondary prevention therapy. All study staff and patients were masked to treatment group allocation. The primary outcome was a five-point composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospital admission for unstable angina, and hospital admission for heart failure, analysed in the intention-to-treat population (all participants randomly assigned to treatment who provided written informed consent). The secondary outcomes were a three-point composite outcome (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke), death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, development of diabetes, and development of impaired renal function. The safety population comprised all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT00829660, and the International Standard Randomised Controlled Trial Number registry, number ISRCTN91899513. Between March 20, 2009, and Oct 23, 2015, 6522 patients were randomly assigned and included in the intention-to-treat population, 3272 assigned to acarbose and 3250 to placebo. Patients were followed up for a median of 5·0 years (IQR 3·4-6·0) in both groups. The primary five-point composite outcome occurred in 470 (14%; 3·33 per 100 person-years) of 3272 acarbose group participants and in 479 (15%; 3·41 per 100 person-years) of 3250 placebo group participants (hazard ratio 0·98; 95% CI 0·86-1·11, p=0·73). No significant differences were seen between treatment groups for the secondary three-point composite outcome, death from any cause, cardiovascular death, fatal or non-fatal myocardial infarction, fatal or non-fatal stroke, hospital admission for unstable angina, hospital admission for heart failure, or impaired renal function. Diabetes developed less frequently in the acarbose group (436 [13%] of 3272; 3·17 per 100 person-years) compared with the placebo group (513 [16%] of 3250; 3·84 per 100 person-years; rate ratio 0·82, 95% CI 0·71-0·94, p=0·005). Gastrointestinal disorders were the most common adverse event associated with drug discontinuation or dose changes (215 [7%] of 3263 patients in the acarbose group vs 150 [5%] of 3241 in the placebo group [p=0·0007]; safety population). Numbers of non-cardiovascular deaths (71 [2%] of 3272 vs 56 [2%] of 3250, p=0·19) and cancer deaths (ten [<1%] of 3272 vs 12 [<1%] of 3250, p=0·08) did not differ between groups. In Chinese patients with coronary heart disease and impaired glucose tolerance, acarbose did not reduce the risk of major adverse cardiovascular events, but did reduce the incidence of diabetes. Bayer AG.

Baseline and long-term gamma-glutamyltransferase, heart failure and cardiac arrhythmias in middle-aged Finnish men: Prospective study and pooled analysis of published evidence.

To assess the associations of baseline and long-term gamma-glutamyltransferase (GGT) activity with risk of heart failure (HF), ventricular arrhythmias (VAs) and atrial fibrillation (AF). GGT measurements were made in a prospective cohort of 1780 men free of HF and cardiac arrhythmias at baseline. Correction for within-person variability was made using data from repeat measurements taken several years apart. During an average follow-up of 22 years, 222 HF, 56 VA and 336 AF events occurred. The regression dilution ratio of loge GGT was 0.68 (95% confidence interval (CI): 0.61-0.74). Serum GGT was log-linearly associated with risk of HF, VAs and AF. In analyses adjusted for established risk factors, the hazard ratios (HRs) (95% CIs) for HF, VAs and AF per 1 SD higher baseline loge GGT values were 1.25 (1.07-1.45), 1.37 (1.04-1.80) and 1.04 (0.92-1.18), respectively. After correction for within-person variability, the corresponding HRs were 1.38 (1.11-1.73), 1.58 (1.06-2.37) and 1.06 (0.88-1.27), respectively. These findings remained consistent in analyses accounting for incident coronary heart disease and the development of impaired renal function. In a meta-analysis of five population-based studies, the fully adjusted relative risks for HF per 1 SD higher baseline and long-term GGT values were 1.28 (1.20-1.35) and 1.43 (1.31-1.56), respectively. In a pooled analysis of two studies, the corresponding risks for AF were 1.09 (1.02-1.16) and 1.14 (1.03-1.25), respectively. GGT is positively and log-linearly associated with future risk of HF, VAs and AF. Further research is needed in order to assess the causal relevance of these findings.

Serum Free Light Chains Identify Patients With Monoclonal Gammopathy At Increased Risk Of Developing Renal Disease

BackgroundMonoclonal gammopathy (MG) is frequently associated with kidney disease (monoclonal gammopathy of renal significance; MGRS). International guidelines recommend the use of the serum free light chain (FLC) assay when screening for monoclonal gammopathies; an abnormal FLC ratio and an elevation of at least one FLC isotype indicates an Ig LC clone. However it is not known if, in patients with normal kidney function, the presence of a FLC clone predisposes to the future development of kidney disease. Patients and MethodsA 22485 patient database with multiple laboratory tests and up to 15-year follow up (Regional Medical Laboratory, Tulsa, OK, USA) was analysed. There were 425 confirmed MG patients with no progression to multiple myeloma. Median age was 72 years (22-97 years) and M/F ratio was 177/248. FLC kappa and lambda were measured nephelometrically with Freelite® (The Binding Site Ltd, Birmingham, UK). Baseline was defined on the first available FLC measurement; this was available at inception in 258 (61%) patients and during follow-up in 167 (39%) patients. 128 patients with MG and an eGFR <60ml/min/1.75m2 and/or a clinical diagnosis of renal disease (ICD9 code) prior to and up to 100 days after baseline were excluded from the analysis. Statistical analyses, including Receiver Operating Characteristics (ROC) to identify monoclonal FLC (iFLC) cut-off were carried out using SPSS v21. Results297 (of 425) patients had a MG with normal renal function at baseline; 118 (40%) patients had an abnormal FLC ratio (88 kappa, median: 35.5 (7.7-2675) mg/L; 30 lambda, median: 83.6 (0.9-3552) mg/L). 21/297 (7%) patients developed renal impairment during the course of follow up (median: 852 (114-2388) days); 15/21 (71%) had monoclonal FLC production. In these patients there was no association between iFLC (median: 47.8 (0.9-3552) mg/L) and creatinine (median: 0.9 (0.5-1.5) mg/dL) levels (p=0.3966). Time to renal impairment (TTRI) was significantly shorter for patients with an abnormal v normal FLC ratio (75% TTRI: 1261 days v not reached (NR), hazard ratio (HR): 5.31; p<0.001). Age between groups was similar (median: 68 (22-97) v 72 (39-92) years; p=0.0544). In 118 patients withan abnormal FLC ratio, Cox regression analysis identified iFLC concentrations as being associated with the development of impaired renal function (p=0001). Furthermore, patients with iFLC>100mg/L (n=25) were at a significantly increased risk of developing renal impairment compared with patients with iFLC<100mg/L (n=93) (75% TTRI: 874 days v NR, respectively; HR: 6.10; p<0.001). ConclusionsThese results indicate that the presence of an Ig LC clone is associated with an increased risk of people with MG and normal kidney function progressing to renal disease. Disclosures:No relevant conflicts of interest to declare.

The obese uremic patient: a newcomer in the nephrology clinic?

This issue of the journal contains a description of three cases of impaired renal function, associated with the use of the anti-obesity drug Xenical® (orlistat) [1]. This drug has been used for more than two decades and the safety profile of orlistat, which is only absorbed to about 1%, is very well established. However, as the authors point out, this is the reason to suspect that, in some rare cases, orlistat may be the underlying reason for the development of impaired renal function and, as also suggested by the authors, there are also plausible mechanisms to explain this unfortunate development. The problem is not new and has been addressed elsewhere [2, 3]. The association of a drug used for the treatment of obesity with the development of impaired renal function, opens for an inevitable discussion about the imminent arrival of the obese subject with uremia on the clinical stage. During recent years, obesity has emerged as an upcoming risk factor associated with chronic kidney disease. In the past, patients with endstage renal disease would generally be in a catabolic situation and weight problems were not an issue. However, with the exploding obesity epidemic all over the world, there is a welldocumented increase in the prevalence of type 2 diabetes, and in a subgroup of obese patients with type 2 diabetes, the associated cardiovascular complications will lead to not only myocardial infarction and stroke, but also to impairment of the renal function, eventually leading to uremia, dialysis and transplantation [4, 5]. This is a new clinical situation which nephrologists have to face and address. Over recent years, treatment of obesity in patients with chronic kidney disease has become an issue, which doctors have never been used to in the past. Just like other clinicians trying to develop strategies to fight obesity in general, nephrologists will be confronted, since it is well known that weight loss has marked positive effects on type 2 diabetes and may even cause reversal of the disease. However, the treatment modalities for obesity are unfortunately not well developed. The classical treatment programmes consisting of diet, exercise and behaviour modification have been tried and do work under certain conditions. Generally, the short-term effects are quite acceptable in the hands of capable therapists, but the long-term results are not too promising. Very low calorie diets (VLCD) have been tried in general populations and seem to offer an interesting alternative. In a recent programme in an outpatient setting, the weight loss after 1 year was quite impressive as was weight loss maintenance [6]. Clearly, there is a role for VLCD programmes in obese individuals and such individuals also with type 2 diabetes, and this opportunity has not been fully utilised in the primary health care sector. The VLCD programmes fill a void of treatment strategies between the standard diet exercise and behaviour modification programme and the most advanced form of obesity therapy, which is bariatric surgery. It is now well established that bariatric surgery will reduce mortality in severely obese patients and improve several of the associated risk factors [7]. The first impressive results were generally associated with the improvement in glycaemic control, which was maintained for several years after bariatric surgery. Weight loss after surgery would also result in blood pressure reduction and improved lipid control, but these risk factors would begin to reappear again a few years after surgery. Summarising the results after up to 18 years of follow-up, it can be said that bariatric surgery has reduced overall mortality

Pancreas Transplant as Treatment to Arrest Renal Function Decline in Patients With Type 1 Diabetes and Proteinuria

Recent findings from the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications study showed that long-term improved glycemic control in patients with type 1 diabetes with normal renal function and normoalbuminuria can delay development of impaired renal function by at least 6.5 years, although the reduction in the relative risk of end-stage renal disease (ESRD) was not significant. The unanswered question is: can improvement of glycemic control delay the onset of ESRD in patients with established diabetic nephropathy? In this context, pancreas transplantation (PATx) can be considered the most effective intervention to restore normoglycemia. Can this aggressive/experimental intervention be applied to arrest/retard renal function decline? To answer this question, this review summarizes the relevant findings from observational studies conducted in cohorts of patients, followed up for 4 to 15 years, who underwent PATx. These noncontrolled studies provided positive answers to the earlier question, principally concerning a significant decrease in albumin excretion levels. However, current drugs used to prevent rejection could impair renal function, principally in recipients with low pretransplant estimated glomerular filtration rate (ie, <60 mL/min). Unfortunately, all these studies had shortcuts that qualify interpretation of the findings. First, it is unclear how much initial estimated glomerular filtration rate loss results from nephrotoxic effect of antirejection drugs, and how much results from improved glycemia and its impact on the reduction of hyperfiltration. Second, the study designs did not consider the wide variation in rates of renal function loss observed in patients with established nephropathy (ie, one third are nonprogressors, one third are slow progressors, and one third are rapid progressors). Third, all studies were observational in nature and clinical trials are needed to properly evaluate the effectiveness of normalization of hyperglycemia through PATx on postponing the onset of ESRD in type 1 diabetes.

Is plasma renin activity a biomarker for the prediction of renal and cardiovascular outcomes in treated hypertensive patients? Observations from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)

Plasma renin activity (PRA) has been shown to predict future cardiovascular (CV) events in observational studies and in clinical trials and to be associated with the prevalence of chronic renal disease in hypertensive subjects. In a nested case-control study, we explored the relationship between CV and renal outcomes and all-cause mortality with baseline measurements of PRA among hypertensive adults randomized in the ASCOT trial. In the UK and Ireland, ASCOT included 9098 hypertensive adults randomized to either calcium channel blocker (CCB)- or β-blocker (BB)-based treatment. Four thousand eight hundred and fifty-three patients with total cholesterol ≤6.5 mmol/L (250 mg/L) were further randomized to atorvastatin or placebo. Over 5.5 years, there were 399 CV events (fatal coronary heart disease (CHD), non-fatal myocardial infarction, coronary revascularization, and fatal and non-fatal stroke), 96 cases of new-onset renal impairment, and 220 deaths. Cases were age, sex, and ethnicity matched with 1525 controls. Conditional logistic regression models were used to evaluate the association between CV events, renal impairment, all-cause mortality, and PRA. For those on antihypertensive (AHT) treatment at the baseline (91.5%), PRA was influenced by prior drug treatment. The median (inter-quartile range; ng/mL/h) levels were 1.04 (0.52, 1.3) for BBs, 1.30 (0.78, 2.72) for CCBs, 1.56 (0.91, 3.50) for diuretics, and 2.33 (1.30, 5.57) for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Odds ratios (OR) and 95% confidence intervals (CIs) for CV and other events were estimated for 1-SD increase in log-transformed PRA levels and by categorizing PRA into quartiles with the lowest as the referent category. Baseline PRA did not predict CV events in models adjusted for baseline characteristics [OR 0.92 (CI 0.81, 1.06, P = 0.25)] and for pre-randomized AHT treatment [OR 0.91 (CI 0.79, 1.04, P = 0.17)] and was not associated with all-cause mortality [OR 1.12 (CI 0.92, 1.37, P = 0.25) and OR 1.06 (CI 0.91, 1.24, P = 0.46)] in the fully adjusted model. Baseline levels of PRA were positively but non-significantly associated with the development of renal impairment in models adjusted for baseline characteristics [OR 1.39 (CI 0.97, 1.97, P = 0.07)] and also for pre-randomized antihypertensive (AHT) treatment [OR 1.35 (CI 0.95, 1.94, P = 0.10)]. Quartile analyses, however, demonstrated a significant positive association of higher levels of PRA with the development of impaired renal function (P = 0.03 and 0.05 in adjusted models, respectively) compared with the lowest quartile. These analyses suggest an association between elevated baseline PRA and the subsequent development of renal impairment but do not support its use to predict future CV events or all-cause mortality in treated hypertensive patients without diagnosed CHD.

E0673 Stent implantation before cardiac surgery with cardiopulmonary bypass has no effect on impaired renal function in patients with renal artery stenosis

ObjectiveTo investigate whether stent implantation before cardiac surgery with cardiopulmonary bypass (CPB) have any effect on the development of impaired renal function in patients with renal artery stenosis (RAS).MethodsIn this...

Assessing the effects of low dose aspirin on uricacid and renal function in healthy adults

Objective: To evaluate the effects of low daily aspirin doses on uric acid (UA) level and renal functions in healthy adults. Methods: Healthy adults were randomized to receive 100 mg (n= 33), or 300 mg (n = 31) aspirin daily for one month. Laboratory tests included measurement of blood urea nitrogen (BUN), serum creatinine, and uric acid (UA) levels. Urine creatinine, urea and uric acid excretion were measured in a 24 h collection of urine, 24 hours urine uric acid, creatinine clearance (Ccr), were measured at baseline and then after 4 weeks of therapy. Results: After 4 weeks of therapy, 100 and 300 mg/d dosage, aspirin caused a 7% and 12% decrease in the rate of UA excretion respectively (P< 0.05). Patients at the dosage 300 mg/d but not the 100mg/day had an increase in serum levels of uric acid (UA), creatinine and urea with a significant decrease in 24 hour creatinine clearance and urinary urea excretion (P<0.05) when compared with the baseline. Conclusion: Because of the effects of 300 mg dose aspirin, in the lowering of kidney function and the potential of aspirin to cause dose-dependent impairment of renal function, patients taking low-dose aspirin therapy should be monitored for the development of impaired renal function.

Individual Differences in Cyclosporine A Pharmacokinetics and Its Association with Acute Renal Function Following Heart Transplantation

Background: The secondary metabolites of cyclosporine A (CsA), AM19, AM1c and AM1c9, have been indi- cated to be nephrotoxic. The aim of the present pilot study was to investigate the relationship between acute renal failure and CsA metabolite levels, including relevant pharmacokinetic genotypes, following heart transplantation. Methods: Whole-blood samples were drawn the first posttransplant week in 22 patients (median 54 years, range from 27 to 65). Whole blood concentrations of CsA and its six main metabolites were analyzed with a validated HPLC-MS/MS method, and relevant CYP3A5 and ABCB1 genotypes determined. Renal function was monitored daily during the first posttransplant month and also at months 3, 6 and 12. Results: One patient died early posttransplant. Six patients were in need of dialysis directly after transplantation. Nine pa- tients developed sustained impaired renal function, while six had stable renal function. Sustained renal impairment tended to be associated with high levels of toxic metabolites (P=0.08). Six of the patients with possible ABCB1 TTT-haplotype developed renal impairment (P=0.12). Conclusion: The present study indicates that toxic CsA metabolites seems to be associated with development of impaired renal function and together with ABCB1 genotyping they might be promising biomarkers for optimalization of immuno- suppressive drug treatment in future studies.

INTRA‐ABDOMINAL PRESSURE AND RENAL FUNCTION AFTER SURGERY TO THE ABDOMINAL AORTA

It has been suggested that an elevated intra-abdominal pressure (IAP) can impair renal function. In a prospective longitudinal study, the IAP of 42 patients admitted to an intensive care unit after abdominal aortic surgery was monitored. When compared with the other patients, the 22 patients (53%) who developed renal impairment had higher IAP (17.8 +/- 6.0 mmHg versus 14.1 +/- 4.8 mmHg; P less than 0.01) and APACHE II scores (15.6 +/- 6.0 versus 9.8 +/- 4.6; P less than 0.01). Each of the 10 patients who were re-explored because of haemodynamic instability and oliguria had an IAP of greater than 18 mmHg (positive predictive value = 85%, negative predictive value = 62%). Following re-exploration, the urinary output increased by 115 +/- 40 mL/h (P less than 0.01), and the IAP decreased by 10 +/- 3 mmHg (P less than 0.01). Although it is concluded that an IAP greater than 18 mmHg is a significant risk factor for the development of impaired renal function, it was not possible to prove a causal relationship between these events. Nevertheless, such a relationship has been demonstrated in animal and human models.

Renal functional changes in experimental cystic disease are tubular in origin

Chronic (30 weeks) structural and functional changes were correlated in diphenylthiazole (DPT)-induced polycystic kidney disease (PKD) in rats. DPT induced two different types of progressive tubular changes: cystic transformation and hyperplastic/atrophic tubular changes. Cystic changes diffusely involved collecting tubules in the outer medulla and cortex, and they were progressive over 30 weeks. Hyperplastic/atrophic changes occurred as clusters of tubules in the cortex and involved between 25% and 50% of tubular profiles after 12 and 30 weeks of drug treatment. Thus, the two types of tubular change were independent of each other and represent different cellular responses to the drug. DPT treatment induced no detectable light- and electron-microscopic or histochemical alterations in glomeruli or renal blood vessels. Renal functional changes consisted of: (1) early (4 weeks) and persistent impairment of concentrating ability; (2) a progressive drop in creatinine clearance and elevation in BUN; and (3) the late onset (30 weeks) of moderate proteinuria. These findings suggest that cystic as well as hyperplastic-atrophic tubular changes contribute to the loss of tubular and renal function in DPT-induced PKD. Both types of tubular lesions may have a role in the development of impaired renal function in other forms of experimental and clinical PKD.

Growth pattern and dietary intake of children with chronic renal insufficiency.

The growth pattern and dietary intake of 33 children with varying degrees of renal insufficiency has been investigated. The development of impaired renal function in infancy has a more deleterious effect on linear growth than has its onset in later years. A reduction in growth velocity may occur once the glomerular filtration rate falls below 25 ml/min/1.73m(2). There was a significant reduction of the energy, protein, and vitamin D intakes of children with renal insufficiency compared with those recommended for their age, and of energy intake compared with that of normal children of their own height. Reduced growth velocity occurred when energy intake fell below 80% of that recommended. The reduction in the intake of energy and nutrients in these children may in part be responsible for their growth retardation.

Analgesic consumption and impaired renal function

Data on 6407 consecutive medical patients admitted to hospital have been analyzed to assess the relationship between regular analgesic ingestion and impaired renal function. A history of daily oral analgesic use was given by 461 patients (7.2 per cent). From the data presented we conclude that the frequency of renal damage was not significantly higher among regular analgesic consumers, when compared with occasional analgesic consumers or patients who denied consumption of analgesics. In addition, there was no evidence of a relationship between increasing duration of daily analgesic consumption and renal disease, except in the case of females over age 60 yr, where the presence of white blood cells in the urine was associated with increasing duration of daily analgesic use; this finding may have occurred by chance, however. The data provide no evidence of a causal association between analgesic consumption and the subsequent development of impaired renal function.

Management of emergencies. V. Acute renal failure.

ACUTE renal failure is a general term for the sudden development of impaired renal function from any of a number of causes (Table 1).Although oliguria (less than 300 or 400 ml. of urine per day) or anuria is usually present azotemia sometimes develops rapidly despite normal urinary output.DiagnosisAn important early step in management is to look for reversible or specifically treatable causes of acute renal failure, such as circulatory failure, obstruction, acute pyelonephritis, certain nephrotoxins and hypercalcemia. The urinary volume may be helpful in differential diagnosis. Complete anuria suggests obstruction or cortical necrosis; it occasionally occurs in . . .