Adeera Levin

Mathematical Formulation to Help Identify the Patient at Risk of Ischemic Tissue Necrosis -A Potentially Lethal Complication of Chronic Renal Failure

Ischemic tissue necrosis (ITN) has been described as a complication of hyperparathyroidism (HPT) in patients with end-stage renal disease (ESRD) and is associated with a mortality rate of up to 80%. Early recognition of ITN is important but difficult. Optimal treatment is controversial. Based on an analysis of the English literature and a recent clinical experience, a mathematical expression to aid in the identification of high-risk patients (2 x [CaPO(4) - 5] x alkaline phosphatase x PTH ratio) was developed. The values for this expression were calculated in 3 recently reported cases and our case (n = 4). The values were compared with those of a group of 54 hyperparathyroid chronic hemodialysis patients (controls); the mean values were significantly different (p < 0.001). The expression, consisting of 4 easily measured laboratory values, appears to differentiate patients with this complication of ITN from patients with only severe HPT. Ten new additional cases were evaluated using the equation; the sensitivity of the equation was 80% and the specificity 92%, positive predictive value was 66% and the negative predictive value 96%. Long-term validation of this equation is required but it appears to be discriminatory and, thus, promising, given the potentially lethal consequences of ITN.

Clinical factors associated with initiation of renal replacement therapy in critically ill patients with acute kidney injury—A prospective multicenter observational study

PURPOSEnOur objective was to describe the current practice for initiation of RRT in this population. There is uncertainty regarding the optimal time to initiate renal replacement therapy (RRT) in critically ill patients with acute kidney injury (AKI).nnnMETHODSnProspective study of patients receiving RRT in 6 intensive care units (ICUs) at 3 hospitals from July 2007 to August 2008. We characterized factors associated with start of RRT and evaluated their relationship with mortality.nnnRESULTSnWe included 234 patients. RRT was initiated 1 day (0-4) after ICU admission (median [interquartile range]). Median creatinine was 331 μmol/L (225-446 μmol/L), urea 22.9 mmol/L (13.9-32.9 mmol/L), and RIFLE-Failure in 76.9%. Of traditional indications, Pao(2)/Fio(2) < 200 (54.5%) and oliguria (32.9%) were most common. ICU and hospital mortality were 45.3% and 51.9%, respectively. In adjusted analysis, mortality at RRT initiation was associated with creatinine <332 μmol/L (odds ratio [OR] 2.8; 95% confidence interval [CI] 1.5-5.4), change in urea from admission >8.9 mmol/L (OR 1.8; 95% CI, 1.0-3.4), urine output <82 mL/24 hours (OR 3.0; 95% CI, 1.4-6.5), fluid balance >3.0 L/24 hours (OR 2.3; 95% CI, 1.2-4.5), percentage of fluid overload >5% (OR 2.3; 95% CI, 1.2-4.7), 3 or more failing organs (OR 4.5; 95% CI, 1.2-4.2), Sequential Organ Failure Assessment score >14 (OR 2.3; 95% CI, 1.3-4.3), and start 4 days or more after admission (OR 4.3; 95% CI, 1.9-9.5). Mortality was higher as factors accumulated.nnnCONCLUSIONnIn ICU patients requiring RRT, there was marked variation in factors that influence start of RRT. RRT initiation with fewer clinical triggers was associated with lower mortality. Timing of RRT may modify survival but requires appraisal in a randomized trial.

KDOQI US Commentary on the KDIGO Clinical Practice Guideline for the Prevention, Diagnosis, Evaluation, and Treatment of Hepatitis C in CKD

KDIGO (Kidney Disease: Improving Global Outcomes) is an international initiative with a key mission of developing clinical practice guidelines in the area of chronic kidney disease (CKD). KDIGO recently published evidence-based clinical practice guidelines for the prevention, diagnosis, evaluation, and treatment of hepatitis C virus infection in individuals with CKD. The process of adaptation of international guidelines is an important task that, although guided by general principles, needs to be individualized for each region and country. Therefore, the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (KDOQI) convened a multidisciplinary group to comment on the application and implementation of the KDIGO guidelines for patients with CKD in the United States. This commentary summarizes the process undertaken by this group in considering the guidelines in the context of health care delivery in the United States. Guideline statements are presented, followed by a succinct discussion and annotation of the rationale for the statements. Research recommendations that are of particular interest to the United States are then summarized to highlight future areas of inquiry that would enable updating of the guidelines.

Longitudinal analysis of performance of estimated glomerular filtration rate as renal function declines in chronic kidney disease

BACKGROUNDnNumerous studies have assessed the accuracy of equations estimating glomerular filtration rate (eGFR) from serum creatinine in individuals with chronic kidney disease (CKD) in cross-sectional studies. Limited literature exists, however, on the consistency of performance of these equations in longitudinal studies as renal function declines.nnnMETHODSnRadionucleotide-measured GFR from 155 predialysis patients with stage 3-5 CKD was compared with eGFR derived from four equations [6-variable Modification of Diet in Renal Disease (6-MDRD), 4-variable MDRD (4-MDRD), Cockcroft-Gault (CG) and Cockcroft-Gault equations corrected for body surface area (CGC)] at baseline, 12 and 24 months. Bias (difference between eGFR and measured GFR) was used as a measure of performance. Restricted Maximum Likelihood (REML) models were used to identify variables potentially affecting the performance of estimating equations across time.nnnRESULTSnMean measured GFR (+/-SD) at baseline, 12 and 24 months was 25.9 +/- 10.7, 23.1 +/- 10.6 and 20.3 +/- 10.1 mL/min/1.73 m(2), respectively. There was a statistically significant negative association between bias and GFR for all four estimates (range: -0.76 to -0.71, P < 0.001 for all), indicating worsening underestimation and overestimation at higher and lower GFR, respectively. This negative association significantly reduced over the 24 months (P < 0.001); however, this was largely due to persistent underestimation of eGFR from individuals with GFR >50 mL/min/1.73 m(2). For those with a baseline GFR <50 mL/min/1.73 m(2), the change in bias for any of the four equations over 24 months was <or=1.1 mL/min/1.73 m(2), suggesting relatively preserved performance with time. The MDRD equations showed a sustained advantage in estimating renal function that was more evident as GFR declined.nnnCONCLUSIONnGFR estimates are inexpensive and show an acceptable longitudinal performance for monitoring CKD patients with GFR <50 mL/min/1.73 m(2). Inaccuracies appear more substantial above this level of GFR, and care with interpretation is required.

N-acetylcysteine for prevention of radiographic contrast material-induced nephropathy: is the intravenous route best?

Use of oral N‐acetylcysteine for preventing radiographic contrast material–induced nephropathy (RCIN) has become widespread, despite conflicting results from clinical trials and meta‐analyses. The variability in study results may reflect differences in baseline risks in study patients, hydration regimens, choice of contrast agent, definition of RCIN, and the oral dosage formulation of N‐acetylcysteine used. Injectable N‐acetylcysteine recently has become available in the United States. Although oral N‐acetylcysteine regimens are typically administered during a 48‐hour period, more rapid intravenous administration could offer an important advantage for urgent procedures such as coronary angiography. However, the three published studies in which intravenous N‐acetylcysteine protocols were used have produced divergent results, likely because of substantially different dosage regimens. With few intravenous studies available, clinicians may look to more broadly studied oral regimens to estimate equivalent intravenous dosages. In the oral studies, however, a wide range of formulations were used, and the bioavailability of each product was uncertain. In addition, the intravenous route circumvents first‐pass metabolism, resulting in less glutathione production, perhaps compromising the antioxidant effects of N‐acetylcysteine administration. Overall, little evidence exists that any studied N‐acetylcysteine protocol improves clinical outcomes in terms of reducing length of hospital stay, need for dialysis, or mortality. Furthermore, N‐acetylcysteine may directly affect serum creatinine level, which all clinical trials to date have used as a primary outcome measure. If oral or intravenous N‐acetylcysteine is used with the intention of preventing RCIN, more‐established preventive measures should not be overlooked, including adequate hydration with isotonic saline, avoidance of potentially nephrotoxic drugs, and use of iso‐osmolar radiographic contrast media.

Timing the initiation of renal replacement therapy for acute kidney injury in Canadian intensive care units: a multicentre observational study

PurposeThe optimal timing for starting renal replacement therapy (RRT) in patients with acute kidney injury (AKI) is unknown. Defining current practice is necessary to design interventional trials. We describe the current Canadian practice regarding the timing of RRT initiation for AKI.MethodsAn observational study of patients undergoing RRT for AKI was undertaken at 11 intensive care units (ICUs) across Canada. Data were captured on demographics, clinical and laboratory findings, indications for RRT, and timing of RRT initiation.ResultsAmong 119 consecutive patients, the most common ICU admission diagnosis was sepsis/septic shock, occurring in 54%. At the time of RRT initiation, the median and interquartile range (IQR) serum creatinine level was 322 (221-432) μmol·L−1. The mean (SD) values for other parameters were as follows: Sequential Organ Failure Assessment (SOFA) score 13.4 (4.1), pH 7.25 (0.15), potassium 4.6 (1.0) mmol·L−1. Also, 64% fulfilled the serum creatinine-based criterion for Acute Kidney Injury Network (AKIN) stage 3. Severity of illness, measured using Acute Physiology and Chronic Health Evaluation (APACHE II) and SOFA scores, did not correlate with AKI severity as defined by the serum creatinine-based AKIN criteria. Median (IQR) time from hospital and ICU admission to the start of RRT was 2.0 (1.0-7.0) days and 1.0 (0-2.0) day, respectively.ConclusionPatients admitted to an ICU who were started on RRT generally had advanced AKI, high-grade illness severity, and multiorgan dysfunction. Also, they were started on RRT shortly after hospital presentation. We describe the current state of practice in Canada regarding the initiation of RRT for AKI in critically ill patients, which can inform the designs of future interventional trials.RésuméObjectifLe moment optimal pour commencer le traitement de l’insuffisance rénale (TIR) en cas de lésion rénale aiguë (LRA) est inconnu. Définir les pratiques actuelles est nécessaire pour concevoir des études interventionnelles. Nous décrivons les pratiques canadiennes actuelles concernant la mise en route du TIR en cas de LRA.MéthodesUne étude observationnelle de patients commençant un TIR pour LRA a été entreprise dans onze unités de soins intensifs (USI) à travers le Canada. Les auteurs ont collecté les données démographiques, les constatations cliniques et biologiques, les indications et le moment de début du TIR.RésultatsParmi 119xa0patients consécutifs, le diagnostic le plus fréquent à l’admission en USI a été le sepsis/choc septique, chez 54xa0% d’entre eux. Au moment du début du TIR, la créatinine sérique médiane (écart interquartile) était 322 (221-432) μmol·L−1. Le score SOFA moyen (ET) était 13,4 (4,1), le pH était de 7,25 (0,15), la kaliémie était 4,6 (1,0) mmol·L−1 et 64xa0% des patients répondaient à la définition de LRA de stade 3 du Acute Kidney Injury Network (AKIN), basée sur la créatinine sérique. La gravité de la maladie, mesurée à l’aide des scores APACHE II et SOFA, n’était pas corrélée à la gravité de la LRA définie selon les critères AKIN basés sur la créatinine sérique. Les délais médians (écarts interquartiles) écoulés entre l’hospitalisation ou l’admission dans l’USI et le début du TIR étaient, respectivement, de 2,0 (1,0 à 7,0) jours et 1,0 (0 à 2,0) jours.ConclusionLes patients admis en USI chez qui un TIR était commencé avaient habituellement une LRA avancée, une maladie grave et une défaillance multi-organes; ils ont également reçu un TIR peu de temps après leur arrivée à l’hôpital. Nos constatations décrivent la situation actuelle des pratiques au Canada concernant le début du TIR pour des patients gravement atteints souffrant de LRA; elles pourront servir de base pour la conception d’études interventionnelles futures.

Incidental Atherosclerotic Renal Artery Stenosis in Patients Undergoing Elective Coronary Angiography: Are These Lesions Significant?

Background: Cardiologists often identify atherosclerotic renal artery stenosis (ARAS) during cardiac angiography. The importance of such ‘incidental’ ARAS (iARAS) is not known. The present study sought to describe renal perfusion using non-captopril (baseline) nuclear renograms in patients with iARAS, and to determine characteristics associated with a positive captopril renogram. Methods: Patients presenting for non-emergent coronary angiography between June 2001 and February 2006 were angiographically screened for iARAS. Those with >50% stenosis of one or both renal arteries were referred to nephrology and underwent nuclear renography. Results: 131 patients had renograms. The mean age was 73.2 ±8.1 and median eGFR was 51.2 (40.0, 66.6) ml/min/1.73 m2. 51% had evidence of reduced perfusion to one kidney, of which 13% were discordant with the angiographic lesion. 9% had positive captopril renograms. Captopril renogram positivity was associated with severe unilateral stenosis (p = 0.02). Conclusions: In cardiac patients diagnosed with iARAS, the presence of known anatomic lesions did not correlate with captopril renogram positivity. Uncertainty remains as to whether nuclear renography is a poor functional test in this population, or the lesions are not functionally significant. These results lead us to question both the significance of such lesions, and the utility of conducting renograms in this population.

Rationale for a home dialysis virtual ward: design and implementation

BackgroundHome-based renal replacement therapy (RRT) [peritoneal dialysis (PD) and home hemodialysis (HHD)] offers independent quality of life and clinical advantages compared to conventional in-center hemodialysis. However, follow-up may be less complete for home dialysis patients following a change in care settings such as post hospitalization. We aim to implement a Home Dialysis Virtual Ward (HDVW) strategy, which is targeted to minimize gaps of care.Methods/designThe HDVW Pilot Study will enroll consecutive PD and HHD patients who fulfilled any one of our inclusion criteria: 1. following discharge from hospital, 2. after interventional procedure(s), 3. prescription of anti-microbial agents, or 4. following completion of home dialysis training. Clinician-led telephone interviews are performed weekly for 2xa0weeks until VW discharge. Case-mix (modified Charlson Comorbidity Index), symptoms (the modified Edmonton Symptom Assessment Scale) and patient satisfaction are assessed serially. The number of VW interventions relating to eight pre-specified domains will be measured. Adverse events such as re-hospitalization and health-services utilization will be ascertained through telephone follow-up after discharge from the VW at 2, 4, 12xa0weeks. The VW re-hospitalization rate will be compared with a contemporary cohort (matched for age, gender, renal replacement therapy and co-morbidities). Our protocol has been approved by research ethics board (UHN: 12-5397-AE). Written informed consent for participation in the study will be obtained from participants.DiscussionThis report serves as a blueprint for the design and implementation of a novel health service delivery model for home dialysis patients. The major goal of the HDVW initiative is to provide appropriate and effective supports to medically complex patients in a targeted window of vulnerability.Trial registration(NCT01912001).

Collapsing glomerulopathy coexisting with membranous glomerulonephritis in native kidney biopsies: a report of 3 HIV-negative patients.

Collapsing glomerulopathy (CG), a variant of idiopathic focal segmental glomerulosclerosis (FSGS), can occur in both human immunodeficiency virus (HIV)-positive and HIV-negative patients. Idiopathic membranous glomerulonephritis (MGN) has been reported to coexist with FSGS, but rarely with CG. We report 3 HIV-negative patients (2 men, 1 woman) who developed nephrotic syndrome secondary to MGN complicated by CG, with relatively rapid disease progression despite aggressive therapy.

Development and utility of a multi-dimensional grid to assess individual mineral metabolism control in hemodialysis patients: A potential aid for therapeutic decision making?

A grid was developed to evaluate control of serum calcium, phosphate, and parathyroid hormone levels in hemodialysis patients, based on guideline recommendations (National Kidney Foundation Kidney Disease Outcomes Quality Initiative and Canadian Society of Nephrology), and its face validity was examined in a representative sample of Canadian patients. A retrospective chart review was undertaken in hemodialysis patients from 7 Canadian units. Patients >18 years, on hemodialysis for ≥12 months, and ≥3 parathyroid hormone levels measured ≥1 month apart were included. The grid classified mineral metabolism control as optimal, suboptimal, or poor (mean of 3 measurements). Medication use, hospitalization, and Emergency Department visits were evaluated in relation to grid occupancy. A second comparative analysis of grid occupancy was undertaken on prevalent hemodialysis cases in British Columbia in 2008. Data from 268 patients (mean age 62.3 years) were analyzed. Using National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines, 17.5%, 28.8%, and 53.7% of patients had optimal, suboptimal, and poor control, respectively, of all 3 parameters (calcium, phosphate, and parathyroid hormone). Using Canadian Society of Nephrology criteria, optimal, suboptimal, and poor control rates were 6.3%, 4.2%, and 89.5%, respectively. Poor control was a possible or a probable cause of hospitalization or Emergency Department attendance in 8 patients. Data from British Columbia in 2008 (n=1858) show optimal, suboptimal, and poor control rates of 15.8%, 24.5%, and 59.7%, respectively. Poor mineral metabolism control among Canadian hemodialysis patients is not showing improvement. The therapeutic grid is a valid tool and may help guide therapeutic decisions, quality control initiatives, and patient counseling. http://www.ukidney.com/bone‐and‐mineral‐metabolism‐resource.