Neesh Pannu

Risk of coronary events in people with chronic kidney disease compared with those with diabetes: a population-level cohort study

BACKGROUND Diabetes is regarded as a coronary heart disease risk equivalent-ie, people with the disorder have a risk of coronary events similar to those with previous myocardial infarction. We assessed whether chronic kidney disease should be regarded as a coronary heart disease risk equivalent. METHODS We studied a population-based cohort with measures of estimated glomerular filtration rate (eGFR) and proteinuria from Alberta, Canada. We used validated algorithms based on hospital admission and medical-claim data to classify participants with baseline history of myocardial infarction or diabetes and to ascertain which patients were admitted to hospital for myocardial infarction during follow-up (the primary outcome). For our primary analysis, we defined baseline chronic kidney disease as eGFR 15-59·9 mL/min per 1·73 m(2) (stage 3 or 4 disease). We used Poisson regression to calculate unadjusted rates and relative rates of myocardial infarction during follow-up for five risk groups: people with previous myocardial infarction (with or without diabetes or chronic kidney disease), and (of those without previous myocardial infarction), four mutually exclusive groups defined by the presence or absence of diabetes and chronic kidney disease. FINDINGS During a median follow-up of 48 months (IQR 25-65), 11,340 of 1,268,029 participants (1%) were admitted to hospital with myocardial infarction. The unadjusted rate of myocardial infarction was highest in people with previous myocardial infarction (18·5 per 1000 person-years, 95% CI 17·4-19·8). In people without previous myocardial infarction, the rate of myocardial infarction was lower in those with diabetes (without chronic kidney disease) than in those with chronic kidney disease (without diabetes; 5·4 per 1000 person-years, 5·2-5·7, vs 6·9 per 1000 person-years, 6·6-7·2; p<0·0001). The rate of incident myocardial infarction in people with diabetes was substantially lower than for those with chronic kidney disease when defined by eGFR of less than 45 mL/min per 1·73 m(2) and severely increased proteinuria (6·6 per 1000 person-years, 6·4-6·9 vs 12·4 per 1000 person-years, 9·7-15·9). INTERPRETATION Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events. FUNDING Alberta Heritage Foundation for Medical Research.

Acute kidney injury: an increasing global concern

Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.

Guidelines for the management of chronic kidney disease

New guidelines for the management of chronic kidney disease have been developed by the Canadian Society of Nephrology (Appendix 1 contains the full-text guidelines; available at [www.cmaj.ca/cgi/content/full/179/11/1154/DC1][1]). These guidelines describe key aspects of the management of chronic

Renal replacement therapy in patients with acute renal failure: a systematic review

CONTEXT Acute renal failure requiring dialytic support is associated with a high risk of mortality and substantial morbidity. OBJECTIVES To summarize current evidence guiding provision of dialysis for patients with acute renal failure, to make recommendations for management, and to identify areas in which additional research is needed. DATA SOURCES Systematic searches of peer-reviewed publications in MEDLINE, EMBASE, and All EBM Reviews through October 2007. STUDY SELECTION Randomized controlled trials (RCTs) and prospective cohort studies studying dialytic support in adults with acute renal failure that reported the incidence of clinical outcomes such as mortality, length of stay, need for chronic dialysis, or development of hypotension. DATA EXTRACTION Quality was independently assessed by 2 reviewers using the Jadad score (RCTs) and the Downs and Black checklist (cohort studies). A single reviewer extracted data, which were independently verified by a second reviewer. Results of RCTs were pooled using a random-effects model. DATA SYNTHESIS From 173 retrieved articles, 30 RCTs and 8 prospective cohort studies were eligible. No conclusions could be drawn about optimal indications for or timing of renal replacement. Available data comparing continuous renal replacement therapy (CRRT) with intermittent hemodialysis demonstrated no clinically relevant difference between modalities, including for all-cause mortality (relative risk [RR], 1.10; 95% confidence interval [CI], 0.99-1.23; I2 = 0%) or for the requirement for chronic dialysis treatment in survivors (RR, 0.91; 95% CI, 0.56-1.49; I2 = 0%). For patients treated with CRRT, limited data suggest that bicarbonate may be preferable to other forms of dialysate alkali and that citrate infusion may be an alternative to systemic anticoagulation in patients at high risk of bleeding. Among patients treated with continuous venovenous hemofiltration (CVVHF), the risk of death was lower at doses of 35 mL/kg per hour (RR of death compared with doses of 20 mL/kg per hour, 0.74; 95% CI, 0.63-0.88). The use of unsubstituted cellulosic membranes should be avoided in intermittent hemodialysis (RR of death compared with biocompatible membranes, 1.23; 95% CI, 1.01-1.50). CONCLUSIONS Based on current data, intermittent hemodialysis and CRRT appear to lead to similar clinical outcomes for patients with ARF. If CVVHF is used, a dose of 35 mL/kg per hour should be provided. Given the paucity of good-quality evidence in this important area, additional large randomized trials are needed to evaluate clinically important outcomes.

Oral Phosphate Binders in Patients with Kidney Failure

Hyperphosphatemia, which is nearly universal in kidney failure, is accompanied by low serum levels of vitamin D and hypocalcemia. Without treatment, severe secondary hyperparathyroidism occurs, which may result in painful fractures, brown tumors, and generalized osteopenia. This article reviews the rationale for treatment with oral phosphate binders, discusses evidence supporting the use of available agents, and suggests an approach for clinical practice.

Associations between Hemodialysis Access Type and Clinical Outcomes: A Systematic Review

Clinical practice guidelines recommend an arteriovenous fistula as the preferred vascular access for hemodialysis, but quantitative associations between vascular access type and various clinical outcomes remain controversial. We performed a systematic review of cohort studies to evaluate the associations between type of vascular access (arteriovenous fistula, arteriovenous graft, and central venous catheter) and risk for death, infection, and major cardiovascular events. We searched MEDLINE, EMBASE, and article reference lists and extracted data describing study design, participants, vascular access type, clinical outcomes, and risk for bias. We identified 3965 citations, of which 67 (62 cohort studies comprising 586,337 participants) met our inclusion criteria. In a random effects meta-analysis, compared with persons with fistulas, those individuals using catheters had higher risks for all-cause mortality (risk ratio=1.53, 95% CI=1.41-1.67), fatal infections (2.12, 1.79-2.52), and cardiovascular events (1.38, 1.24-1.54). Similarly, compared with persons with grafts, those individuals using catheters had higher risks for mortality (1.38, 1.25-1.52), fatal infections (1.49, 1.15-1.93), and cardiovascular events (1.26, 1.11-1.43). Compared with persons with fistulas, those individuals with grafts had increased all-cause mortality (1.18, 1.09-1.27) and fatal infection (1.36, 1.17-1.58), but we did not detect a difference in the risk for cardiovascular events (1.07, 0.95-1.21). The risk for bias, especially selection bias, was high. In conclusion, persons using catheters for hemodialysis seem to have the highest risks for death, infections, and cardiovascular events compared with other vascular access types, and patients with usable fistulas have the lowest risk.

An overview of drug-induced acute kidney injury

The complex nature of critical illness often necessitates the use of multiple therapeutic agents, many of which may individually or in combination have the potential to cause renal injury. The use of nephrotoxic drugs has been implicated as a causative factor in up to 25% of all cases of severe acute renal failure in critically ill patients. Acute tubular necrosis is the most common form of renal injury from nephrotoxin exposure, although other types of renal failure may be seen. Given that this is a preventable cause of a potentially devastating complication, a comprehensive strategy should be used to avoid nephrotoxicity in critically ill patients including: accurate estimation of pre-existing renal function using serum creatinine–based glomerular filtration rates, avoidance of nephrotoxins if possible, ongoing monitoring of renal function, and immediate discontinuation of suspected nephrotoxins in the event of renal dysfunction.

Associations Between Acute Kidney Injury and Cardiovascular and Renal Outcomes After Coronary Angiography

Background— Acute kidney injury (AKI) is associated with early mortality after percutaneous coronary revascularization procedures, but its prognostic relevance to long-term clinical outcomes remains controversial. Methods and Results— We conducted a retrospective study of 14 782 adults who received coronary angiography in the province of Alberta, Canada, between 2004 and 2006. AKI was identified on the basis of changes in serum creatinine concentration within 7 days of the procedure according to AKI Network criteria. The associations between AKI and long-term outcomes, including mortality, end-stage renal disease, and cardiovascular and renal hospitalizations, were studied with the use of Cox regression of multiple failure times. The adjusted risk of death increased with increasing severity of AKI; compared with no AKI, the adjusted hazard ratio for death was 2.00 (95% confidence interval, 1.69 to 2.36) with stage 1 AKI and 3.72 (95% confidence interval, 2.92 to 4.76) with stage 2 or 3 AKI. The adjusted risk of end-stage renal disease requiring renal replacement therapy also increased according to the severity of AKI (hazard ratio, 4.15 [95% confidence interval, 2.32 to 7.42] and 11.74 [95% confidence interval, 6.38 to 21.59], respectively), as did the risks of subsequent hospitalizations for heart failure and acute renal failure. Conclusions— These findings inform the controversy surrounding AKI after angiography, demonstrating that it is a significant risk factor for long-term mortality, end-stage renal disease, and hospitalization for cardiovascular and renal events after coronary angiography.

International Society of Nephrology's 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology

Executive summary Acute kidney injury (AKI) is a major contributor to poor patient outcomes. AKI occurs in about 13·3 million people per year, 85% of whom live in the developing world, and, although no direct link between AKI and death has yet been shown, AKI is thought to contribute to about 1·7 million deaths every year. The course of AKI varies with the setting in which it occurs, and the severity and duration of AKI aff ects outcomes such as dialysis requirement, renal functional recovery, and survival. Recognition is increasing for the eff ect of AKI on patients, and the resulting societal burden from its longterm eff ects, including development of chronic kidney disease and end-stage renal disease needing dialysis or trans plantation. Few systematic eff orts to manage (prevent, diagnose, and treat) AKI have been put in place and few resources have been allocated to inform health-care professionals and the public of the importance of AKI as a preventable and treatable disease. Several factors have contributed to the paucity of information. Most importantly, there have been few population-level epidemiological studies in several regions of the world. Diffi culties in defi nition of the incidence of AKI are especially evident in searches for data from low-income and middle-income countries, where more than 85% of the world’s population resides. No nationwide data collection systems are available, and data are usually from isolated centres and probably largely underestimate the true extent of AKI because they mostly do not include patients with AKI who were not able to reach a hospital for treatment. A recent metaanalysis that included 312 cohort studies and more than 49 million patients shows a scarcity of data from Africa and large parts of southeast Asia. We did an updated meta-analysis that used the most recent KDIGO (Kidney Disease: Improving Global Outcomes) defi nitions, which confi rms the high incidence and resulting outcomes of AKI, particularly in Africa, Asia, and Latin America, for which data were previously absent. The strong relation between the severity of AKI and consequent mortality is reiterated by our fi ndings and is evident across heterogeneous populations and specifi c disease cohorts. However, large gaps remain in knowledge about the factors that aff ect the geographical variation of AKI and poor outcomes. Many diff erences exist in the aetiology, pathophysiology, and management of AKI across the world. In high-income countries, AKI develops mainly in patients in hospitals. In low-income and middle-income countries, AKI occurs mainly in the community setting in acute illness, usually in association with diarrhoeal states and dehydration, infections such as malaria, and toxins (venoms and poisons). Public health issues (eg, contaminated water, poor sanitation, endemic infections such as malaria and dengue fever, venomous snakes, and toxic traditional medicines) and socioeconomic factors (eg, availability of health-care facilities) aff ect the epidemiology of AKI. Additionally availability of trained personnel and access to diagnostic tests and dialysis aff ect practice patterns and impose barriers to care. The extent to which these factors contribute to mortality and non-recovery of renal function has not been quantifi ed. AKI is potentially preventable and treatable with timely intervention, but there continues to be a high human burden. Which specifi c factors account for the poor outcomes and to what extent variations in care delivery contribute are unclear. The ability to provide lifesaving treatments for AKI provides a compelling argument to consider therapy for AKI as much of a basic right as it is to give antiretroviral drugs to treat HIV in low-resource regions, especially because care needs only be given for a Published Online March 13, 2015 http://dx.doi.org/10.1016/ S0140-6736(15)60126-X

Epidemiology of Acute Kidney Injury

BACKGROUND AND OBJECTIVES The worldwide incidence of acute kidney injury is poorly known because of underreporting, regional disparities, and differences in definition and case mix. New definitions call for revision of the problem with unified criteria. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This article reports on the research recommendations of an international multidisciplinary committee, assembled to define a research agenda on acute kidney injury epidemiology using a modified three-step Delphi process. RESULTS Knowledge of incidence and risk factors is crucial because it drives local and international efforts on detection and treatment. Also, notable differences exist between developing and developed countries: Incidence seems higher in the former, but underreporting compounded by age and gender disparities makes available data unreliable. In developing countries, incidence varies seasonally; incidence peaks cause critical shortages in medical and nursing personnel. Finally, in developing countries, lack of systematic evaluation of the role of falciparum malaria, obstetric mechanisms, and hemolytic uremic syndrome on acute kidney injury hampers efforts to prevent acute kidney injury. CONCLUSIONS The committee concluded that epidemiologic studies should include (1) prospective out- and inpatient studies that measure incidence of community and hospital acute kidney injury and post-acute kidney injury chronic kidney disease; (2) incidence measurements during seasonal peaks in developing and developed countries; and (3) whenever available, use of reliable existing administrative or institutional databases. Epidemiologic studies using standardized definitions in community and institutional settings in developing and underdeveloped countries are essential first steps to achieving early detection and intervention and improved patient outcomes.