Cinacalcet Treatment of Primary Hyperparathyroidism

Although parathyroidectomy remains the only curative approach to most primary hyperparathyroidism cases, medical treatment with cinacalcet HCl has been proven to be a reasonable alternative for several patient subgroups. Cinacalcet almost always controls hypercalcemia and hypophosphatemia sufficiently. PTH levels are lowered, and cognitive parameters improve. While an increase in bone mineral density DEXA scan scores was not demonstrated in cinacalcet trials, the same applies to more than half of patients after parathyroidectomy. Medical therapy should be first choice in patients with hyperplasia in all glands rather than an isolated adenoma (10–15%), patients with persisting HPT following unsuccessful surgery or inoperable cases due to comorbidities, and patients detected in lab screens for hypercalcemia before developing symptoms who should be treated early but are usually reluctant to undergo surgery. Nephrolithiasis was not found to occur more frequently in cinacalcet trial groups, but urine calcium excretion as one major risk factor of this complication of primary HPT may increase on cinacalcet. Patients carrying the rs1042636 polymorphism of the calcium-sensing receptor gene respond more sensitively to cinacalcet and have a higher risk of calcium stone formation. Cinacalcet is usually administered twice daily but three or four doses per day should be discussed to mimic the beneficial pulsatile PTH-pattern

Disease severity adversely affects delivery of dialysis in acute renal failure

Background/Aims: Methods of intermittent hemodialysis (IHD) dose quantification in acute renal failure (ARF) are not well defined. This observational study was designed to evaluate the impact of disease activity on delivered single pool Kt/V-urea in ARF patients. Methods: 100 patients with severe ARF (acute intrinsic renal disease in 18 patients, nephrotoxic acute tubular necrosis in 38 patients, and septic ARF in 44 patients) were analyzed during four consecutive sessions of IHD, performed for 3.5-5 h every other day or daily. Target IHD dose was a single pool Kt/V-urea of 1.2 or more per dialysis session for all patients. Prescribed Kt/V-urea was calculated from desired dialyzer clearance (K), desired treatment time (t) and anthropometric estimates for urea distribution volume (V). The desired clearance (K) was estimated from prescribed blood flow rate and manufacturer's charts of in vivo data obtained in maintenance dialysis patients. Delivered single pool Kt/V-urea was calculated using the Daugirdas equation. Results: None of the patients had prescription failure of the target dose. The delivered IHD doses were substantially lower than the prescribed Kt/V values, particularly in ARF patients with sepsis/septic shock. Stratification according to disease severity revealed that all patients with isolated ARF, but none with 3 or more organ failures and none who needed vasopressive support received the target dose. Conclusion: Prescription of target IHD dose by single pool Kt/V-urea resulted in suboptimal dialysis dose delivery in critically ill patients. Numerous patient-related and treatment-immanent factors acting in concert reduced the delivered dose. Copyright (C) 2007 S. Karger AG, Basel

What is the real impact of acute kidney injury?

Background: Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting. The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. Methods: A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. Results: The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. Conclusions: This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI

Malnutrition and inflammation in acute kidney injury due to earthquake-related crush syndrome

<p>Abstract</p> <p>Background</p> <p>Malnutrition and inflammation are common and serious complications in patients with acute kidney injury (AKI). However, the profile of these complications in patients with AKI caused by crush syndrome (CS) remains unclear. This study describes the clinical characteristics of malnutrition and inflammation in patients with AKI and CS due to the Wenchuan earthquake.</p> <p>Methods</p> <p>One thousand and twelve victims and eighteen healthy adults were recruited to the study. They were divided into five groups: Group A was composed of victims without CS and AKI (904 cases); Group B was composed of patients with CS and AKI who haven't received renal replacement therapy (RRT) (57 cases); and Group C was composed of patients with CS and AKI receiving RRT (25 cases); Group D was composed of earthquake victims with AKI but without CS (26 cases); and Group E was composed of 18 healthy adult controls. The C-reactive protein (CRP), prealbumin, transferrin, interleukin-6 and TNF-α were measured and compared between Group E and 18 patients from Group C.</p> <p>Results</p> <p>The results indicate that participants in Group C had the highest level of serum creatinine, blood urea nitrogen and uric acid. Approximately 92% of patients with CS who had RRT were suffering from hypoalbuminemia. The interleukin-6 and CRP levels were significantly higher in patients with CS AKI receiving RRT than in the control group. Patients in Group C received the highest dosages of albumin, plasma or red blood cell transfusions. One patient in Group C died during treatment.</p> <p>Conclusions</p> <p>Malnutrition and inflammation was common in patients with earthquake-related CS and had a negative impact on the prognosis of these subjects. The results of this study indicate that the use of RRT, intensive nutritional supplementation and transfusion alleviated the degree of malnutrition and inflammation in hemodialysis patients with crush syndrome.</p

The assessment, serial evaluation, and subsequent sequelae of acute kidney injury (ASSESS-AKI) study: design and methods

<p>Abstract</p> <p>Background</p> <p>The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors.</p> <p>Methods</p> <p>The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis.</p> <p>Conclusions</p> <p>ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI.</p

Difference between pre-operative and cardiopulmonary bypass mean arterial pressure is independently associated with early cardiac surgery-associated acute kidney injury

<p>Abstract</p> <p>Background</p> <p>Cardiac surgery-associated acute kidney injury (CSA-AKI) contributes to increased morbidity and mortality. However, its pathophysiology remains incompletely understood. We hypothesized that intra-operative mean arterial pressure (MAP) relative to pre-operative MAP would be an important predisposing factor for CSA-AKI.</p> <p>Methods</p> <p>We performed a prospective observational study of 157 consecutive high-risk patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The primary exposure was delta MAP, defined as the pre-operative MAP minus average MAP during CPB. Secondary exposure was CPB flow. The primary outcome was early CSA-AKI, defined by a minimum RIFLE class - RISK. Univariate and multivariate logistic regression were performed to explore for association between delta MAP and CSA-AKI.</p> <p>Results</p> <p>Mean (± SD) age was 65.9 ± 14.7 years, 70.1% were male, 47.8% had isolated coronary bypass graft (CABG) surgery, 24.2% had isolated valve surgery and 16.6% had combined procedures. Mean (± SD) pre-operative, intra-operative and delta MAP were 86.6 ± 13.2, 57.4 ± 5.0 and 29.4 ± 13.5 mmHg, respectively. Sixty-five patients (41%) developed CSA-AKI within in the first 24 hours post surgery. By multivariate logistic regression, a delta MAP≥26 mmHg (odds ratio [OR], 2.8; 95%CI, 1.3-6.1, p = 0.009) and CPB flow rate ≥54 mL/kg/min (OR, 0.2, 0.1-0.5, p < 0.001) were independently associated with CSA-AKI. Additional variables associated with CSA-AKI included use of a side-biting aortic clamp (OR, 3.0; 1.3-7.1, p = 0.012), and body mass index ≥25 (OR, 4.2; 1.6-11.2, p = 0.004).</p> <p>Conclusion</p> <p>A large delta MAP and lower CPB flow during cardiac surgery are independently associated with early post-operative CSA-AKI in high-risk patients. Delta MAP represents a potentially modifiable intra-operative factor for development of CSA-AKI that necessitates further inquiry.</p

Validation of a case definition to define chronic dialysis using outpatient administrative data

<p>Abstract</p> <p>Background</p> <p>Administrative health care databases offer an efficient and accessible, though as-yet unvalidated, approach to studying outcomes of patients with chronic kidney disease and end-stage renal disease (ESRD). The objective of this study is to determine the validity of outpatient physician billing derived algorithms for defining chronic dialysis compared to a reference standard ESRD registry.</p> <p>Methods</p> <p>A cohort of incident dialysis patients (Jan. 1 - Dec. 31, 2008) and prevalent chronic dialysis patients (Jan 1, 2008) was selected from a geographically inclusive ESRD registry and administrative database. Four administrative data definitions were considered: at least 1 outpatient claim, at least 2 outpatient claims, at least 2 outpatient claims at least 90 days apart, and continuous outpatient claims at least 90 days apart with no gap in claims greater than 21 days. Measures of agreement of the four administrative data definitions were compared to a reference standard (ESRD registry). Basic patient characteristics are compared between all 5 patient groups.</p> <p>Results</p> <p>1,118,097 individuals formed the overall population and 2,227 chronic dialysis patients were included in the ESRD registry. The three definitions requiring at least 2 outpatient claims resulted in kappa statistics between 0.60-0.80 indicating "substantial" agreement. "At least 1 outpatient claim" resulted in "excellent" agreement with a kappa statistic of 0.81.</p> <p>Conclusions</p> <p>Of the four definitions, the simplest (at least 1 outpatient claim) performed comparatively to other definitions. The limitations of this work are the billing codes used are developed in Canada, however, other countries use similar billing practices and thus the codes could easily be mapped to other systems. Our reference standard ESRD registry may not capture all dialysis patients resulting in some misclassification. The registry is linked to on-going care so this is likely to be minimal. The definition utilized will vary with the research objective.</p