Sofia B. Ahmed

Overview of the Alberta Kidney Disease Network

BackgroundThe Alberta Kidney Disease Network is a collaborative nephrology research organization based on a central repository of laboratory and administrative data from the Canadian province of Alberta.DescriptionThe laboratory data within the Alberta Kidney Disease Network can be used to define patient populations, such as individuals with chronic kidney disease (using serum creatinine measurements to estimate kidney function) or anemia (using hemoglobin measurements). The administrative data within the Alberta Kidney Disease Network can also be used to define cohorts with common medical conditions such as hypertension and diabetes. Linkage of data sources permits assessment of socio-demographic information, clinical variables including comorbidity, as well as ascertainment of relevant outcomes such as health service encounters and events, the occurrence of new specified clinical outcomes and mortality.ConclusionThe unique ability to combine laboratory and administrative data for a large geographically defined population provides a rich data source not only for research purposes but for policy development and to guide the delivery of health care. This research model based on computerized laboratory data could serve as a prototype for the study of other chronic conditions.

Intermittent Hypoxia Increases Arterial Blood Pressure in Humans Through a Renin-Angiotensin System-Dependent Mechanism

Intermittent hypoxia (IH) is believed to contribute to the pathogenesis of hypertension in obstructive sleep apnea through mechanisms that include activation of the renin-angiotensin system. The objective of this study was to assess the role of the type I angiotensin II receptor in mediating an increase in arterial pressure associated with a single 6-hour IH exposure. Using a double-blind, placebo-controlled, randomized, crossover study design, we exposed 9 healthy male subjects to sham IH, IH with placebo medication, and IH with the type I angiotensin II receptor antagonist losartan. We measured blood pressure, cerebral blood flow, and ventilation at baseline and after exposure to 6 hours of IH. An acute isocapnic hypoxia experimental protocol was conducted immediately before and after exposure to IH. IH with placebo increased resting mean arterial pressure by 7.9±1.6 mm Hg, but mean arterial pressure did not increase with sham IH (1.9±1.5 mm Hg) or with losartan IH (−0.2±2.4 mm Hg; P<0.05). Exposure to IH prevented the diurnal decrease in the cerebral blood flow response to hypoxia, independently of the renin-angiotensin system. Finally, in contrast to other models of IH, the acute hypoxic ventilatory response did not change throughout the protocol. IH increases arterial blood pressure through activation of the type I angiotensin II receptor, without a demonstrable impact on the cerebrovascular or ventilatory response to acute hypoxia.

Declining Kidney Function Increases the Prevalence of Sleep Apnea and Nocturnal Hypoxia

BACKGROUND Sleep apnea is an important comorbidity in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Although the increased prevalence of sleep apnea in patients with ESRD is well established, few studies have investigated the prevalence of sleep apnea in patients with nondialysis-dependent kidney disease, and no single study, to our knowledge, has examined the full spectrum of kidney function. We sought to determine the prevalence of sleep apnea and associated nocturnal hypoxia in patients with CKD and ESRD. We hypothesized that the prevalence of sleep apnea would increase progressively as kidney function declines. METHODS Two hundred fifty-four patients were recruited from outpatient nephrology clinics and hemodialysis units. All patients completed an overnight cardiopulmonary monitoring test to determine the prevalence of sleep apnea (respiratory disturbance index ≥ 15) and nocturnal hypoxia (oxygen saturation < 90% for ≥ 12% of monitoring). Patients were stratified into three groups based on estimated glomerular filtration rate (eGFR) as follows: eGFR ≥ 60 mL/min/1.73 m(2) (n = 55), CKD (eGFR < 60 mL/min/1.73 m(2) not on dialysis, n = 124), and ESRD (on hemodialysis, n = 75). RESULTS The prevalence of sleep apnea increased as eGFR declined (eGFR ≥ 60 mL/min/1.73 m(2), 27%; CKD, 41%; ESRD, 57%; P = .002). The prevalence of nocturnal hypoxia was higher in patients with CKD and ESRD (eGFR ≥ 60 mL/min/1.73 m(2), 16%; CKD, 47%; ESRD, 48%; P < .001). CONCLUSIONS Sleep apnea is common in patients with CKD and increases as kidney function declines. Almost 50% of patients with CKD and ESRD experience nocturnal hypoxia, which may contribute to loss of kidney function and increased cardiovascular risk.

Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

Intermittent hypoxia (IH) is thought to be responsible for many of the long‐term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir = 45.0 mmHg) alternating with 2 min of normoxia (peak = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA.

A Randomized Trial Comparing Buttonhole with Rope Ladder Needling in Conventional Hemodialysis Patients

BACKGROUND AND OBJECTIVES Buttonhole needling is reported to be associated with less pain than standard needling. The purpose of this study was to compare patient perceived pain and fistula complications in buttonhole and standard needling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS In this study, 140 conventional hemodialysis patients were randomly assigned to buttonhole or standard needling. The primary outcome was patient perceived pain with needling at 8 weeks. Fistula complications of hematoma, bleeding postdialysis, and infection were tracked. RESULTS Median pain score at 8 weeks using a visual analog scale from 0 to 10 cm was similar for standard and buttonhole needling (1.2 [0.4-2.4] versus 1.5 [0.5-3.4]; P=0.57). Rate of hematoma formation in standard needling was higher (436 versus 295 of 1000 hemodialysis sessions; P=0.03). Rate of no bleeding postdialysis was 23.6 and 28.3 per 1000 in standard and buttonhole needling, respectively (P=0.40). Rate of localized signs of infection in standard versus buttonhole needling was 22.4 versus 50 per 1000 (P=0.003). There was one episode of Staphylococcal aureus bacteremia during the 8 weeks with buttonhole needling and no episodes with standard needling (P=1.00). Within 12 months of follow-up, another two buttonhole needling episodes developed S. aureus bacteremia, and nine buttonhole needling episodes had needling site abscesses requiring intravenous antibiotics versus zero standard needling episodes (P=0.003). CONCLUSIONS Patients had no difference in pain between buttonhole and standard needling. Although fewer buttonhole needling patients developed a hematoma, there was an increased risk of bacteremia and localized signs of infection. Routine use of buttonhole needling is associated with increased infection risk.

Body Mass Index and Angiotensin-Dependent Control of the Renal Circulation in Healthy Humans

Obesity is increasingly recognized as a risk factor for renal disease, but the mechanism is unclear. Renal plasma flow response to captopril, as an index of renin-angiotensin system activity, was measured by para-aminohippurate clearance technique in 100 healthy, normotensive subjects in balance on a high-salt diet. Of the 100 subjects, body mass index exceeded 25 in 56 and exceeded 30 in 22. The average vasodilator response to captopril was 27±7 mL/min per 1.73 m2 (P<0.0001). After adjustment for other predictors of the renal plasma flow response to captopril using a multivariate linear regression model, there was a highly significant relationship between age- and plasma renin activity–adjusted body mass index and the renal plasma flow response to captopril; however, a quadratic model provided a substantially better fit (r=0.55; P<0.0001; P=0.03 versus linear correlation). The strong association between increasing body mass index and angiotensin-dependent control of the renal circulation suggests that this may be a mechanism by which obesity contributes to renal disease. Weight loss should be considered in the overweight or obese patient for renal protection.

Access to health care among status Aboriginal people with chronic kidney disease

Background: Ethnic disparities in access to health care and health outcomes are well documented. It is unclear whether similar differences exist between Aboriginal and non-Aboriginal people with chronic kidney disease in Canada. We determined whether access to care differed between status Aboriginal people (Aboriginal people registered under the federal Indian Act) and non-Aboriginal people with chronic kidney disease. Methods: We identified 106 511 non-Aboriginal and 1182 Aboriginal patients with chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m2). We compared outcomes, including hospital admissions, that may have been preventable with appropriate outpatient care (ambulatory-care–sensitive conditions) as well as use of specialist services, including visits to nephrologists and general internists. Results: Aboriginal people were almost twice as likely as non-Aboriginal people to be admitted to hospital for an ambulatory-care–sensitive condition (rate ratio 1.77, 95% confidence interval [CI] 1.46–2.13). Aboriginal people with severe chronic kidney disease (estimated glomerular filtration rate < 30 mL/min/1.73 m2) were 43% less likely than non-Aboriginal people with severe chronic kidney disease to visit a nephrologist (hazard ratio 0.57, 95% CI 0.39–0.83). There was no difference in the likelihood of visiting a general internist (hazard ratio 1.00, 95% CI 0.83–1.21). Interpretation: Increased rates of hospital admissions for ambulatory-care–sensitive conditions and a reduced likelihood of nephrology visits suggest potential inequities in care among status Aboriginal people with chronic kidney disease. The extent to which this may contribute to the higher rate of kidney failure in this population requires further exploration.

Nocturnal Hypoxia and Loss of Kidney Function

Background Although obstructive sleep apnea (OSA) is more common in patients with kidney disease, whether nocturnal hypoxia affects kidney function is unknown. Methods We studied all adult subjects referred for diagnostic testing of sleep apnea between July 2005 and December 31 2007 who had serial measurement of their kidney function. Nocturnal hypoxia was defined as oxygen saturation (SaO2) below 90% for ≥12% of the nocturnal monitoring time. The primary outcome, accelerated loss of kidney function, was defined as a decline in estimated glomerular filtration rate (eGFR) ≥4 ml/min/1.73 m2 per year. Results 858 participants were included and followed for a mean study period of 2.1 years. Overall 374 (44%) had nocturnal hypoxia, and 49 (5.7%) had accelerated loss of kidney function. Compared to controls without hypoxia, patients with nocturnal hypoxia had a significant increase in the adjusted risk of accelerated kidney function loss (odds ratio (OR) 2.89, 95% confidence interval [CI] 1.25, 6.67). Conclusion Nocturnal hypoxia was independently associated with an increased risk of accelerated kidney function loss. Further studies are required to determine whether treatment and correction of nocturnal hypoxia reduces loss of kidney function.

Lifetime Risk of ESRD

Lifetime risk is the cumulative risk of experiencing an outcome between a disease-free index age and death. The lifetime risk of ESRD for a middle-aged individual is a relevant and easy to communicate measure of disease burden. We estimated lifetime risk of ESRD in a cohort of 2,895,521 adults without ESRD from 1997 to 2008. To estimate lifetime risk of ESRD by level of baseline kidney function, we analyzed a cohort of participants who had a serum creatinine measurement. We also estimated the sex- and index age-specific lifetime risk of incident ESRD and accounted for the competing risk of death. Among those individuals without ESRD at age 40 years, the lifetime risk of ESRD was 2.66% for men and 1.76% for women. The risk was higher in persons with reduced kidney function: for eGFR=44-59 ml/min per 1.73 m(2), the lifetime risk of ESRD was 7.51% for men and 3.21% for women, whereas men and women with relatively preserved kidney function (eGFR=60-89 ml/min per 1.73 m(2)) had lifetime risks of ESRD of 1.01% and 0.63%, respectively. The lifetime risk of ESRD was consistently higher for men at all ages and eGFR strata compared with women. In conclusion, approximately 1 in 40 men and 1 in 60 women of middle age will develop ESRD during their lifetimes (living into their 90s). These population-based estimates may assist individuals who make decisions regarding public health policy.

Management of patients with acute hyperkalemia

A 72-year-old man presents to his family physician for follow-up of hypertension, reporting fatigue and generalized weakness. His medical history also includes peptic ulcer disease, type 2 diabetes mellitus and chronic kidney disease. The estimated glomerular filtration rate is 30 mL/min per 1.73 m2