Ziv Harel

Gastrointestinal Adverse Events with Sodium Polystyrene Sulfonate (Kayexalate) Use: A Systematic Review

BACKGROUND Sodium polystyrene sulfonate (Kayexalate; Sanofi-Aventis, Paris, France) is a cation-exchange resin routinely used in the management of hyperkalemia. However, its use has been associated with colonic necrosis and other fatal gastrointestinal adverse events. Although the addition of sorbitol to sodium polystyrene sulfonate preparations was previously believed to be the cause of gastrointestinal injury, recent reports have suggested that sodium polystyrene sulfonate itself may be toxic. Our objective was to systematically review case reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. METHODS MEDLINE (1948 to July 2011), EMBASE (1980 to July 2011), Cochrane Central Register of Controlled Trials (CENTRAL) (1993 to July 27, 2011), bibliographies of identified articles, and websites of relevant drug agencies and professional associations in the United States and Canada were reviewed to identify eligible reports of adverse gastrointestinal events associated with sodium polystyrene sulfonate use. Causality criteria of the World Health Organization causality assessment system were applied to each report. RESULTS Thirty reports describing 58 cases (41 preparations containing sorbitol and 17 preparations without sorbitol) of adverse events were identified. The colon was the most common site of injury (n=44; 76%), and transmural necrosis (n=36; 62%) was the most common histopathologic lesion reported. Mortality was reported in 33% of these cases due to gastrointestinal injury. CONCLUSIONS Sodium polystyrene sulfonate use, both with and without sorbitol, may be associated with fatal gastrointestinal injury. Physicians must be cognizant of the risk of these adverse events when prescribing this therapy for the management of hyperkalemia.

The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study*.

Objective:Among critically ill patients with acute kidney injury, the impact of renal replacement therapy modality on long-term kidney function is unknown. Compared with conventional intermittent hemodialysis, continuous renal replacement therapy may promote kidney recovery by conferring greater hemodynamic stability; yet continuous renal replacement therapy may not enhance patient survival and is resource intense. Our objective was to determine whether continuous renal replacement therapy was associated with a lower risk of chronic dialysis as compared with intermittent hemodialysis, among survivors of acute kidney injury. Design:Retrospective cohort study. Setting:Linked population-wide administrative databases in Ontario, Canada. Patients:Critically ill adults who initiated dialysis for acute kidney injury between July 1996 and December 2009. In the primary analysis, we considered those who survived to at least 90 days after renal replacement therapy initiation. Interventions:Initial receipt of continuous renal replacement therapy versus intermittent hemodialysis. Measurements and Main Results:Continuous renal replacement therapy recipients were matched 1:1 to intermittent hemodialysis recipients based on a history of chronic kidney disease, receipt of mechanical ventilation, and a propensity score for the likelihood of receiving continuous renal replacement therapy. Cox proportional hazards were used to evaluate the relationship between initial renal replacement therapy modality and the primary outcome of chronic dialysis, defined as the need for dialysis for a consecutive period of 90 days. We identified 2,315 continuous renal replacement therapy recipients of whom 2,004 (87%) were successfully matched to 2,004 intermittent hemodialysis recipients. Participants were followed over a median duration of 3 years. The risk of chronic dialysis was significantly lower among patients who initially received continuous renal replacement therapy versus intermittent hemodialysis (hazard ratio, 0.75; 95% CI, 0.65–0.87). This relation was more prominent among those with preexisting chronic kidney disease (p value for interaction term = 0.065) and heart failure (p value for interaction term = 0.035). Conclusions:Compared with intermittent hemodialysis, initiation of continuous renal replacement therapy in critically ill adults with acute kidney injury is associated with a lower likelihood of chronic dialysis.

Nephrologist follow-up improves all-cause mortality of severe acute kidney injury survivors

Survivors of severe acute kidney injury remain at high risk of death well after apparent recovery from the initial insult. Here we determine whether early nephrology follow-up after a hospitalization complicated by severe acute kidney injury associates with patient survival. This consisted of a cohort study of all hospitalized adults in Ontario from 1996 to 2008 with acute kidney injury who received temporary inpatient dialysis and survived for 90 days following discharge independent from dialysis. Propensity scores were used to match individuals with early nephrology follow-up, defined as a visit with a nephrologist within 90 days of discharge, to those without. The outcome was time to all-cause mortality of 3877 patients who met the eligibility criteria within a maximum follow-up of 2 years. A total of 1583 patients had early nephrology follow-up of whom 1184 were successfully matched 1:1 to those not receiving early follow-up. The incidence of all-cause mortality was lower in those patients with early nephrology follow-up compared with those without (8.4 compared with 10.6 per 100-patient years, hazard ratio 0.76 (95% CI: 0.62-0.93)). Thus, early nephrology follow-up after hospitalization with acute kidney injury and temporary dialysis was associated with improved survival. This finding requires definitive testing in a randomized controlled trial.

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis.

Objective To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011. Study selection Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes. Results 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89). Conclusion Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.

Risk of Chronic Dialysis and Death Following Acute Kidney Injury

BACKGROUND Acute kidney injury frequently arises within an acute care hospitalization. Outcomes among acute kidney injury survivors following hospital discharge are poorly documented. METHODS We conducted a population-based cohort study between 1996 and 2006 of all adult patients in Ontario with acute kidney injury who did not require in-hospital dialysis, and who survived free of dialysis ≥30 days after discharge. Those with acute kidney injury (n=41,327) were matched 1:1 to patients without acute kidney injury during their index hospitalization. Matching was by age (±1 year), sex, history of chronic kidney disease, receipt of mechanical ventilation during the index hospitalization, and a propensity score for developing acute kidney injury. The primary outcome was subsequent need for chronic dialysis. The secondary outcomes were all-cause mortality and rehospitalization. RESULTS Mean age was 70 years, and median follow-up was 2 years (maximum 10 years). The incidence of chronic dialysis was 1.78 per 100 person-years among those with acute kidney injury and 0.74 per 100 person-years among unaffected controls (adjusted hazard ratio [HR]; 2.70, 95% confidence interval [CI], 2.42-3.00). Rates also were higher for all-cause mortality (15.34 vs 14.51 per-100 person-years; adjusted HR 1.10; 95% CI, 1.07-1.13) and rehospitalization (44.93 vs 37.18 per 100 person-years; adjusted HR 1.21; 95% CI, 1.18-1.24). CONCLUSION Even when acute dialysis is not required, survivors of acute kidney injury remain at higher risk of receipt of chronic dialysis thereafter. The absolute risk of death was more than 8 times the rate of chronic dialysis.

Detecting chronic kidney disease in population-based administrative databases using an algorithm of hospital encounter and physician claim codes

BackgroundLarge, population-based administrative healthcare databases can be used to identify patients with chronic kidney disease (CKD) when serum creatinine laboratory results are unavailable. We examined the validity of algorithms that used combined hospital encounter and physician claims database codes for the detection of CKD in Ontario, Canada.MethodsWe accrued 123,499 patients over the age of 65 from 2007 to 2010. All patients had a baseline serum creatinine value to estimate glomerular filtration rate (eGFR). We developed an algorithm of physician claims and hospital encounter codes to search administrative databases for the presence of CKD. We determined the sensitivity, specificity, positive and negative predictive values of this algorithm to detect our primary threshold of CKD, an eGFR <45 mL/min per 1.73 m2 (15.4% of patients). We also assessed serum creatinine and eGFR values in patients with and without CKD codes (algorithm positive and negative, respectively).ResultsOur algorithm required evidence of at least one of eleven CKD codes and 7.7% of patients were algorithm positive. The sensitivity was 32.7% [95% confidence interval: (95% CI): 32.0 to 33.3%]. Sensitivity was lower in women compared to men (25.7 vs. 43.7%; p <0.001) and in the oldest age category (over 80 vs. 66 to 80; 28.4 vs. 37.6 %; p < 0.001). All specificities were over 94%. The positive and negative predictive values were 65.4% (95% CI: 64.4 to 66.3%) and 88.8% (95% CI: 88.6 to 89.0%), respectively. In algorithm positive patients, the median [interquartile range (IQR)] baseline serum creatinine value was 135 μmol/L (106 to 179 μmol/L) compared to 82 μmol/L (69 to 98 μmol/L) for algorithm negative patients. Corresponding eGFR values were 38 mL/min per 1.73 m2 (26 to 51 mL/min per 1.73 m2) vs. 69 mL/min per 1.73 m2 (56 to 82 mL/min per 1.73 m2), respectively.ConclusionsPatients with CKD as identified by our database algorithm had distinctly higher baseline serum creatinine values and lower eGFR values than those without such codes. However, because of limited sensitivity, the prevalence of CKD was underestimated.

The Frequency and Characteristics of Dietary Supplement Recalls in the United States

cess to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Both authors. Acquisition of data: Bothauthors. Analysis and interpretation of data: Both authors. Drafting of the manuscript: Both authors. Critical revision of the manuscript for important intellectual content: Both authors. Administrative, technical, and material support: Both authors. Study supervision: Both authors. Conflict of Interest Disclosures: None reported.

Risk prediction models for contrast induced nephropathy: systematic review

Objectives To look at the available literature on validated prediction models for contrast induced nephropathy and describe their characteristics. Design Systematic review. Data sources Medline, Embase, and CINAHL (cumulative index to nursing and allied health literature) databases. Review methods Databases searched from inception to 2015, and the retrieved reference lists hand searched. Dual reviews were conducted to identify studies published in the English language of prediction models tested with patients that included derivation and validation cohorts. Data were extracted on baseline patient characteristics, procedural characteristics, modelling methods, metrics of model performance, risk of bias, and clinical usefulness. Eligible studies evaluated characteristics of predictive models that identified patients at risk of contrast induced nephropathy among adults undergoing a diagnostic or interventional procedure using conventional radiocontrast media (media used for computed tomography or angiography, and not gadolinium based contrast). Results 16 studies were identified, describing 12 prediction models. Substantial interstudy heterogeneity was identified, as a result of different clinical settings, cointerventions, and the timing of creatinine measurement to define contrast induced nephropathy. Ten models were validated internally and six were validated externally. Discrimination varied in studies that were validated internally (C statistic 0.61-0.95) and externally (0.57-0.86). Only one study presented reclassification indices. The majority of higher performing models included measures of pre-existing chronic kidney disease, age, diabetes, heart failure or impaired ejection fraction, and hypotension or shock. No prediction model evaluated its effect on clinical decision making or patient outcomes. Conclusions Most predictive models for contrast induced nephropathy in clinical use have modest ability, and are only relevant to patients receiving contrast for coronary angiography. Further research is needed to develop models that can better inform patient centred decision making, as well as improve the use of prevention strategies for contrast induced nephropathy.

Rehospitalizations and Emergency Department Visits after Hospital Discharge in Patients Receiving Maintenance Hemodialysis

Clinical outcomes after a hospital discharge are poorly defined for patients receiving maintenance in-center (outpatient) hemodialysis. To describe the proportion and characteristics of these patients who are rehospitalized, visit an emergency department, or die within 30 days after discharge from an acute hospitalization, we conducted a population-based study of all adult patients receiving maintenance in-center hemodialysis who were discharged between January 1, 2003, and December 31, 2011, from 157 acute care hospitals in Ontario, Canada. For patients with more than one hospitalization, we randomly selected a single hospitalization as the index hospitalization. Of the 11,177 patients included in the final cohort, 1926 (17%) were rehospitalized, 2971 (27%) were treated in the emergency department, and 840 (7.5%) died within 30 days of discharge. Complications of type 2 diabetes mellitus were the most common reason for rehospitalization, whereas heart failure was the most common reason for an emergency department visit. In multivariable analysis using a cause-specific Cox proportional hazards model, the following characteristics were associated with 30-day rehospitalization: older age, the number of hospital admissions in the preceding 6 months, the number of emergency department visits in the preceding 6 months, higher Charlson comorbidity index score, and the receipt of mechanical ventilation during the index hospitalization. Thus, a large proportion of patients receiving maintenance in-center hemodialysis will be readmitted or visit an emergency room within 30 days of an acute hospitalization. A focus on improving care transitions from the inpatient setting to the outpatient dialysis unit may improve outcomes and reduce healthcare costs.

Predictors of progression to chronic dialysis in survivors of severe acute kidney injury: a competing risk study

BackgroundSurvivors of acute kidney injury are at an increased risk of developing irreversible deterioration in kidney function and in some cases, the need for chronic dialysis. We aimed to determine predictors of chronic dialysis and death among survivors of dialysis-requiring acute kidney injury.MethodsWe used linked administrative databases in Ontario, Canada, to identify patients who were discharged from hospital after an episode of acute kidney injury requiring dialysis and remained free of further dialysis for at least 90 days after discharge between 1996 and 2009. Follow-up extended until March 31, 2011. The primary outcome was progression to chronic dialysis. Predictors for this outcome were evaluated using cause-specific Cox proportional hazards models, and a competing risk approach was used to calculate absolute risk.ResultsWe identified 4 383 patients with acute kidney injury requiring temporary in-hospital dialysis who survived to discharge. After a mean follow-up of 2.4 years, 356 (8%) patients initiated chronic dialysis and 1475 (34%) died. The cumulative risk of chronic dialysis was 13.5% by the Kaplan-Meier method, and 10.3% using a competing risk approach. After accounting for the competing risk of death, previous nephrology consultation (subdistribution hazard ratio (sHR) 2.03; 95% confidence interval (CI) 1.61-2.58), a history of chronic kidney disease (sHR3.86; 95% CI 2.99-4.98), a higher Charlson comorbidity index score (sHR 1.10; 95% CI 1.05-1.15/per unit) and pre-existing hypertension (sHR 1.82; 95% CI 1.28-2.58) were significantly associated with an increased risk of progression to chronic dialysis.ConclusionsAmong survivors of dialysis-requiring acute kidney injury who initially become dialysis independent, the subsequent need for chronic dialysis is predicted by pre-existing kidney disease, hypertension and global comorbidity. This information can identify patients at high risk of progressive kidney disease who may benefit from closer surveillance after cessation of the acute phase of illness.