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Background: Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist., Methods: To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m 2 ). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria)., Results: We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding., Conclusions: These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice., (Copyright © 2021 by the American Society of Nephrology.)

Background and Objectives: Data from observational and interventional studies provide discordant results regarding the relationship between creatinine increase after renin-angiotensin system inhibition (RASi) and adverse outcomes. We compared health outcomes among patients with different categories of increase in creatinine upon initiation of RASi in a large population-based cohort., Design, Setting, Participants, & Measurements: We performed a retrospective analysis of the Stockholm CREAtinine Measurements database, which contains complete information on diagnoses, medication dispensation claims, and laboratory test results for all Stockholm citizens accessing health care. Included were 31,951 adults initiating RASi during 2007-2011 with available pre- and postinitiation creatinine monitoring. Multivariable Cox regression was used to compare mortality, cardiovascular and ESKD events among individuals with different ranges of creatinine increases within 2 months after starting treatment., Results: In a median follow-up of 3.5 years, acute increases in creatinine were associated with mortality (3202 events) in a graded manner: compared with creatinine increases <10%, a 10%-19% increase showed an adjusted hazard ratio (HR) of 1.15 (95% confidence interval [95% CI], 1.05 to 1.27); HR 1.22 (95% CI, 1.07 to 1.40) for 20%-29%; HR 1.55 (95% CI, 1.36 to 1.77) for ≥30%. Similar graded associations were present for heart failure (2275 events, P <0.001) and ESKD (52 events; P <0.001), and, less consistently, myocardial infarction (842 events, P= 0.25). Results were robust across subgroups, among continuing users, when patients with decreases in creatinine were excluded from the reference group, and after accounting for death as a competing risk., Conclusions: Among real-world monitored adults, increases in creatinine (>10%) after initiation of RASi are associated with worse health outcomes. These results do not address the issue of discontinuation of RASi when plasma creatinine increases but do suggest that patients with increases in creatinine have higher subsequent risk of cardiovascular and kidney outcomes., (Copyright © 2019 by the American Society of Nephrology.)

Introduction: Continued progression of kidney disease will lead to renal function too low to sustain healthy life. In developed countries, such people will be offered renal replacement therapy in the form of dialysis or renal transplantation. Requirement for dialysis or transplantation is termed end-stage renal disease (ESRD)., Methods and Outcomes: We conducted a systematic review, aiming to answer the following clinical questions: What are the effects of a low-sodium diet to reduce progression rate of chronic kidney disease? What are the effects of a low-protein diet to reduce progression rate of chronic kidney disease? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview)., Results: We found seven studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions., Conclusions: In this systematic overview we present information relating to the effectiveness and safety of the following interventions: low-protein diet versus control, different low-protein diets versus each other (low-protein diet versus very low-protein diet), low-sodium diet versus control, different low-sodium diets versus each other.

Background: Sodium intake is an important determinant of blood pressure; therefore, reduction of intake may be an attractive population-based target for chronic kidney disease (CKD) prevention. Most guidelines recommend sodium intake of < 2.3 g/day, based on limited evidence. We reviewed the association between sodium intake and renal outcomes., Methods: We reviewed cohort studies and clinical trials, which were retrieved by searching electronic databases, that evaluated the association between sodium intake/excretion and measures of renal function, proteinuria, or new need for dialysis., Results: Of 4,337 reviewed citations, seven (n = 8,129) were eligible, including six cohort studies (n = 7,942) and one clinical trial (n = 187). Four studies (n = 1,787) included patients with CKD. All four cohort studies reported that high intake (> 4.6 g/day) was associated with adverse outcomes (vs. moderate/low), while none reported an increased risk with moderate intake (vs. low). Three studies (n = 6,342) included patients without CKD. Two cohort studies (n = 6,155) reported opposing directions of association between low (vs. moderate) sodium intake and renal outcomes, and one clinical trial (n = 187) reported a benefit from low intake (vs. moderate) on proteinuria but an adverse effect on serum creatinine., Conclusions: Available, but limited, evidence supports an association between high sodium intake (> 4.6g/day) and adverse outcomes. However, the association with low intake (vs. moderate) is uncertain, with inconsistent findings from cohort studies. There is urgent need to clarify the long-term efficacy and safety of currently recommended low sodium intake in patients with CKD., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: The reported incidence, prevalence and outcomes of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) are variable. The risks and benefits of warfarin anticoagulation need to be defined as the risk of bleeding in ESRD patients may overwhelm the benefits of embolic stroke prevention. We undertook a systematic literature review to clarify these issues., Methods: A literature search was undertaken using Medline and EMBASE from 1990 to September 2011. Studies that reported incidence, prevalence or selected outcomes in ESRD patients with AF were included. Cross-sectional, cohort and randomized controlled trials with >25 participants were included. The lists of authors and abstracts from the search were reviewed by two investigators to determine the manuscripts for full text review. Data were abstracted to a form designed specifically for this study. The quality of the studies was assessed using the Newcastle-Ottawa scale. Event rates were calculated using a random-effects model., Results: Twenty-five studies met our inclusion criteria. The prevalence of AF was 11.6% and the overall incidence was 2.7/100 patient-years. The risk of mortality and stroke was increased in ESRD patients with AF at 26.9 and 5.2/100 patient-years versus 13.4 and 1.9/100 patient-years compared with ESRD patients without AF. The majority of studies do not support a protective effect for warfarin in ESRD patients with AF., Conclusions: The incidence and prevalence of AF in ESRD patients are higher than in the general population and are associated with an increased risk of stroke and mortality. An appropriately designed randomized controlled trial is required to determine whether anticoagulation is an appropriate therapeutic strategy in patients with end-stage renal disease and atrial fibrillation.

Atrial fibrillation is prevalent in dialysis patients. Both ischaemic and haemorrhagic stroke are common in patients on dialysis with atrial fibrillation. In the general population, warfarin is highly effective for prophylaxis of ischaemic stroke, and though warfarin use likely increases the risk of intracranial haemorrhage, the absolute increase in risk is small. In the general population, absolute and relative increases in major extracranial bleeding from warfarin use are also both modest. In patients on dialysis, the effectiveness of warfarin as a prophylaxis for ischaemic stroke and its effects on intracranial or extracranial bleeding have not been assessed in randomized trials. Cohort studies vary greatly in their estimates of the magnitude of the increased risk of bleeding from warfarin use. A single cohort study found rates of intracranial haemorrhage in patients on dialysis with atrial fibrillation to be in an order of magnitude that is greater than those in the general population with atrial fibrillation, and that intracranial haemorrhage more than doubled in association with warfarin use. Basic, translational and limited clinical observations also implicate warfarin in the pathogenesis of vascular calcification, which is likely on the causal pathway to patient-important vascular outcomes. Finally, the effect of warfarin on ischaemic stroke in three recent large observational studies has been in the direction of harm, no benefit, and modest, non-statistically significant benefit, respectively. We believe that no clear recommendation can be made between three alternative approaches. It is acceptable to withhold or discontinue warfarin in patients on dialysis, to offer anticoagulants to all dialysis patients without a contraindication whose congestive heart failure, hypertension, age, diabetes and previous stroke or transient ischaemic attack (CHADS(2)) score >1 or 2 and to discuss and individualize prophylaxis on a patient-by-patient basis. Randomized trials of new agents are needed in this area.

Objectives: We will evaluate the effects of bioimpedance analysis-guided fluid management to reduce volume expansion, of vitamin D(3) supplementation, and of the combination of those techniques on decrease of left ventricular mass in peritoneal dialysis (PD) patients., Design: This multicenter randomized controlled trial, with a 2 × 2 factorial design, will be conducted at PD clinics affiliated with 3 Canadian teaching hospitals. Consenting PD patients 18 years of age or older will be included. Patients will be excluded if they have contraindications to bioimpedance or magnetic resonance imaging, life or technique expectancy of less than 1 year, peritonitis within the preceding 3 months, or serum calcium above 2.55 mmol/L., Intervention: The study will randomize 70 patients to bio-impedance-guided volume management or to usual care and to vitamin D(3) 50,000 U weekly for 8 doses, and then 10,000 U weekly or to matching placebo., Main Outcome Measures: The primary outcome will be change in left ventricular mass at 1 year as determined by cardiac magnetic resonance imaging. The secondary outcome will be a composite endpoint of death, nonfatal cardiovascular event, and transfer to hemodialysis for dialysis inadequacy or ultrafiltration failure. Other outcome measures will include blood pressure, quality of life, 6-minute walk test, inflammatory and fibrotic markers and their association with peritoneal membrane transport properties, and residual renal function. Patients will be followed for clinical outcomes for up to 3 years., Conclusions: This study will assess whether bioimpedance-directed volume management and vitamin D(3) supplementation can improve left ventricular mass in PD patients.

Background and Objectives: To determine whether warfarin prolongs the time to first mechanical-catheter failure., Design, Setting, Participants, & Measurements: This was a multicenter parallel-group randomized controlled trial with blinding of participants, trial staff, clinical staff, outcome assessors, and data analysts. Randomization was in a 1:1 ratio in blocks of four and was concealed by use of fax to a central pharmacy. Hemodialysis patients with newly-placed catheters received low-intensity monitored-dose warfarin, target international normalized ratio (INR) 1.5 to 1.9, or placebo, adjusted according to schedule of sham INR results. The primary outcome was time to first mechanical-catheter failure (inability to establish a circuit or blood flow less than 200 ml/min)., Results: We randomized 174 patients: 87 to warfarin and 87 to placebo. Warfarin was associated with a hazard ratio (HR) of 0.90 (P=0.60; 95% confidence interval [CI], 0.57, 1.38) for time to first mechanical-catheter failure. Secondary analyses were: time to first guidewire exchange or catheter removal for mechanical failure (HR 0.78; 95% CI, 0.37, 1.6); time to catheter removal for mechanical failure (HR 0.67; 95% CI, 0.19, 2.37); and time to catheter removal for any cause (HR 0.89; 95% CI, 0.42, 1.81). Major bleeding occurred in 10 participants assigned to warfarin and seven on placebo (relative risk, 1.43; 95% CI, 0.57, 3.58; P=0.61)., Conclusions: We found no evidence for efficacy of low-intensity, monitored-dose warfarin in preventing mechanical-catheter failure., (Copyright © 2011 by the American Society of Nephrology)

Background: In the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET), dual therapy did not reduce cardiovascular or renal outcomes compared with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers alone. Previous controlled trials with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated greater cardiovascular and renal benefit in people with renal risk. We hypothesized that dual therapy would be more effective than monotherapy in patients with low glomerular filtration rate and elevated albuminuria., Methods and Results: Post hoc analysis was performed of renal subgroups of dual therapy versus monotherapy for the ONTARGET study and angiotensin receptor blocker versus placebo for the Telmisartan Randomized Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND). The studies featured hazard ratios by subgroups and Cox regression models with factors for treatment, subgroup, and interactions. The main cardiovascular outcome was the composite of cardiovascular death, myocardial infarction, stroke, or hospitalization for heart failure, and the main renal outcome was the composite of chronic dialysis or doubling of creatinine. In ONTARGET, there was no cardiovascular or renal benefit from dual over monotherapy in any subgroup, even with low glomerular filtration rate and/or elevated albuminuria. In TRANSCEND, in the comparison of angiotensin receptor blocker with placebo, there was a significant interaction for the main renal outcome (P = 0.01) in the direction of harm for patients with normoalbuminuria (0.37 versus 0.16 events per 100 patient-years; hazard ratio, 2.35; confidence interval, 1.33 to 4.15) but a trend to benefit with microalbuminuria (0.52 versus 0.89 events per 100 patient-years; hazard ratio, 0.60; confidence interval, 0.25 to 1.46) and macroalbuminuria (1.57 versus 2.60 events per 100 patient-years; hazard ratio, 0.71; confidence interval, 0.21 to 2.44)., Conclusions: This post hoc analysis does not support dual therapy over monotherapy in high-vascular risk patients with low glomerular filtration rate or albuminuria. This observation is a post hoc comparison and should be interpreted appropriately., Clinical Trial Registration: URL: http://clinicaltrials.gov Identifier: NCT00153101.

Background and Aims: National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that all people with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) undergo evaluation for anaemia and metabolic bone disease. We aim to report the prevalence of metabolic complications in adults with low GFR., Methods: Analysis of 15,802 non-institutionalised adult participants in the Third National Health and Nutrition Survey (NHANES III), a cross-sectional population-based survey conducted in the United States between 1986 and 1994. Renal function was estimated according the modification of diet in renal disease equation 7 (MDRD GFR), the Cockcroft-Gault formula and by the serum creatinine cut-off points described by Couchoud and colleagues. Haemoglobin <110 g/l occurred in 42.2% [95% confidence interval (CI) 28.3-56.0] of patients with MDRD GFR <30 ml/min/1.73 m(2) [stage 3 chronic kidney disease (CKD)] and 3.5% (95% CI 2.4-4.7) of patients with MDRD GFR between 30 and 60 ml/min/1.73 m(2) (stage 4-5 CKD). Corresponding prevalences for calcium <2.15 mmol/l were 8.2 (95% CI 1.6-14.8) and 3.4 (95% CI 1.7-5.2); for phosphate >1.6 mmol/l, 15.1 (95% CI 5.0-25.3) and 0.3 (95% CI 0-0.6); and for bicarbonate <23 mmol/l, 32.7 (95% CI 19.6-45.9) and 5.7 (95% CI 3.3-8.2), respectively. Similar results were obtained when patients were categorised by the Cockcroft-Gault formula or Couchoud's cut-off points., Conclusions: The prevalence of complications in stage 3 CKD is low. These data do not support the recommendation for routine screening for metabolic complications of renal insufficiency in adults seen in primary care settings whose GFR exceeds 30 ml/min/1.73 m(2)., (Copyright 2007 S. Karger AG, Basel.)

Background: Chronic renal insufficiency (CRI) has been identified as an important risk factor for cardiac events. Studies in the United States reported decreased survival and decreased use of surgical and medical interventions after myocardial infarction in patients with CRI., Methods: We studied the impact of renal function on health outcomes in a Canadian cohort of consecutive patients admitted with acute coronary syndrome (ACS) between October 1997 and October 1999. The study design is an observational cohort of 5,549 adult patients who survived to discharge with a discharge diagnosis of ACS. Renal function is classified into 4 levels: (1) normal, glomerular filtration rate (GFR) greater than 80 mL/min/1.73 m2 (>1.33 mL/s); (2) mild CRI, GFR of 60 to 80 mL/min/1.73 m2 (1.00 to 1.33 mL/s); (3) moderate CRI, GFR of 30 to 59 mL/min/1.73 m2 (0.50 to 0.98 mL/s); and (4) severe CRI, GFR less than 30 mL/min/1.73 m2 (<0.50 mL/s). The primary outcome is death., Results: Advanced and moderate CRI independently predicted death (hazard ratio, 1.06; 95% confidence interval [CI], 1.01 to 1.12; and hazard ratio, 1.23; 95% CI, 1.18 to 1.29). Severe anemia (hemoglobin level < 9.0 g/dL [<90 g/L]) also was an independent risk factor for death (hazard ratio, 1.38; 95% CI, 1.18 to 1.61). Use of beta-blockers (hazard ratio, 0.91; 95% CI, 0.86 to 0.97), acetylsalicylic acid (hazard ratio, 0.90; 95% CI, 0.84 to 0.97), lipid-lowering therapy (hazard ratio, 0.84; 95% CI, 0.78 to 0.89), and medical thrombolysis (hazard ratio, 0.89; 95% CI, 0.81 to 0.97) were associated with reduced risk for death. Medical interventions with beta-blockers, acetylsalicylic acid, lipid-lowering therapy, and thrombolysis and surgical intervention were significantly less likely to be used in patients with CRI., Conclusion: Despite universal access to health care, Canadian patients with CRI are more likely to die after a cardiac event and less likely to receive important interventions.

Background: Individuals with end-stage renal disease on hemodialysis therapy have reduced aerobic exercise capacity and reduced muscle strength., Methods: This was a single-blind, randomized, placebo-controlled trial of an exercise intervention in hemodialysis patients administered erythropoietin. The intervention consisted of progressive resisted isotonic quadriceps and hamstrings exercise and training on a cycle ergometer three times weekly for 12 weeks. Individuals in the control group underwent a nonprogressive program of range-of-motion exercises. Both groups were observed for an additional 5 months without intervention. Outcomes were assessed without knowledge of treatment assignment at baseline, 12 weeks, and 5 months. A healthy age- and sex-matched sample provided comparative data., Results: Our sample was relatively high functioning, with a mean score on the Physical Function subscale of the Short Form 36 (SF-36) of 76 of 100. At 12 weeks, there were large and statistically significant differences in favor of the experimental group on the submaximal exercise test (14 W; 95% confidence interval, 2 to 26) and muscle strength (45 lb; 95% confidence interval, 9 to 81), but not in the 6-minute walk, symptoms questionnaire, or SF-36. Differences between the intervention and control groups at 12 weeks were not evident on retesting 5 months after the end of the intervention. Compared with the healthy sample, patients were significantly lower functioning on the submaximal exercise test, muscle strength, and 6-minute walk test at baseline., Conclusion: In this high-functioning sample, the exercise program improved physical impairment measures, but had no effect on symptoms or health-related quality of life. The impact on patients with a greater degree of physical dysfunction needs to be rigorously studied., (Copyright 2002 by the National Kidney Foundation, Inc.)

Polytetrafluoroethylene (PTFE) dialysis grafts in patients with end-stage renal disease (ESRD) are prone to thrombotic failure. The objective of this multicenter, randomized, double-blind, placebo-controlled clinical trial was to determine if warfarin reduces the risk of failure of PTFE dialysis grafts. Patients with ESRD and newly placed PTFE grafts were studied at community and academic dialysis centers in Southwestern Ontario. Patients were allocated to receive warfarin or matching placebo, with the warfarin administered to achieve a target INR of 1.4 to 1.9. Time to graft failure was the main outcome measure. A total of 107 patients (56 allocated to warfarin) were randomized. The time-to-event analysis revealed no significant difference in the likelihood of graft survival between the two groups (odds ratio, 1.76 in favor of placebo; 95% confidence interval, 0.72 to 4.34). Six major bleeds occurred in five patients allocated to warfarin compared with none in the patients who received placebo (P = 0.03). In conclusion, low-dose warfarin was associated with an excess of clinically important major bleeding in patients with ESRD enrolled in this study. Furthermore, low-intensity, monitored-dose warfarin does not appear to prolong PTFE graft survival.

The individual risk of developing end-stage renal disease (ESRD) and its overall impact on life expectancy is not known. This study's objectives were to determine the effect of ESRD on life expectancy for a cohort of 20-yr-olds and to compare this impact to that of several cancers for which population-based screening programs exist. A computer simulation, stratified by race (white, black) and by gender was used to calculate cumulative lifetime risk of ESRD, life-years lost to ESRD, and cumulative Medicare payments for ESRD. Similar calculations were made for breast, prostate, and colorectal cancer. The cumulative lifetime risk of ESRD for a 20-yr-old black woman is 7.8%. Equivalent risks for black men are 7.3%, white men 2.5%, and white women 1.8%. Lost years of life attributable to ESRD are 1.09, 1.10, 0.40, and 0.32 yr for black women, black men, white men, and white women, respectively. In blacks, ESRD is responsible for nearly as much loss of life-years as breast cancer in women and more loss of life-years than colorectal or prostate cancer in men. In addition, treatment costs for ESRD in this population are many-fold more expensive than cumulative treatment costs of these cancers. Exploring new screening and treatment strategies may be warranted to prevent ESRD, particularly in the US black population.

End-stage renal disease is an important and costly health problem. Strategies for its prevention are urgently needed. Knowledge of the population-based prevalence of renal insufficiency in nondiabetic adults would inform such strategies. Black and white nondiabetic adult participants in the Third National Health and Nutrition Examination Survey were analyzed. The analysis was stratified by age, gender, and race, and four clinically applicable methods were used to assess renal function. There were 13,251 complete records for analysis. By the Modification of Diet in Renal Diseases (MDRD) GFR (GFR) prediction Equation 7, 58% (95% confidence interval [CI], 56 to 60%) of the total adult nondiabetic black and white US population had MDRD GFR below 80 ml/min per 1.73m(2), 13% (95% CI, 11 to 14%) below 60 ml/min per 1.73m(2), and 0.26% (95% CI, 0.19 to 0.33%) below 30 ml/min per 1.73m(2). By the Cockcroft-Gault formula, the equivalent figures were 39% (95% CI, 37 to 41%), 14% (95% CI, 12% - 16%), and 0.81% (95% CI, 0.46 to 1.2%), respectively. The findings of an unexpectedly high prevalence of low clearance and the increased prevalence of low clearance with age were consistent across the four clearance estimation methods used and for each race-sex stratum. The absolute magnitude of the prevalence of low clearance was, however, dependent on the clearance method used. Assessed by estimation from serum creatinine, low clearance may be very common, particularly with advancing age. The prognosis (in terms of risk for progression and end-stage renal disease) of low clearance in unreferred populations may differ from that in referred populations and requires further study.

Background: It is ionized calcium that is physiologically active and under homeostatic control; however, total calcium is more conveniently measured. Formulae for correction of calcium to account for albumin binding have not been validated in a dialysis setting., Methods: We measured ionized calcium simultaneously with total calcium (t[Ca]), albumin, total protein and pH before dialysis in 50 stable outpatients and convalescent inpatients., Results: Although 92% of patients were taking calcium supplements and 70% taking alphacalcidol, 11 patients (22%) had ionized hypocalcaemia. To facilitate comparison of calculated ionized calcium, measured total calcium (t[Ca]), and 'corrected' calcium (c[Ca]), with the criterion measure of ionized calcium, all measurements were converted to z scores, standardized on the normal range for each variable. Results are expressed as intraclass correlation coefficients (ICC: 0, all differences are due to error; 1, all differences are due to between patient variation)., Conclusions: None of the published formulae greatly improved the test characteristics beyond simply using the total calcium. A correction formula in widespread use (Payne), quoted in reference texts, agreed less well with ionized calcium than did the unadjusted measured calcium. Correction formulae should be abandoned in favour of the use of uncorrected calcium. In cases of doubt, ionized calcium should be directly measured.

Renal impairment is a recognized risk factor for prolonged hypoglycemia, but predisposing characteristics in patients with advanced renal impairment have not been studied. We observed prolonged hypoglycemia in a number of patients with end-stage renal disease (ESRD) and conducted a case-control study at two Canadian centers to identify such risk factors. Through hospital, pharmacy, and dialysis program records, we retrospectively identified 7 case patients and 31 controls with ESRD and type 2 diabetes using oral hypoglycemic monotherapy. Control patients had no history of hospital admission for prolonged hypoglycemia. All case patients and 28 controls were receiving glyburide (glibenclamide in Europe); the remainder were treated with tolbutamide. Duration of intravenous treatment for hypoglycemia ranged from 28 to 256 hours, with 83 g to 2 kg of glucose administered per episode. Preceding treatment with glyburide varied from 2 days to 13 years. Univariate analyses showed a recent decline in oral intake (odds ratio [OR], 81; 95% confidence interval [CI], 3.6 to 1,840), previous hypoglycemic episodes (OR, 15; 95% CI, 0.77 to 297), longer duration of diabetes (22 versus 12 years; P = 0.008), and a history of cerebrovascular disease (OR, 7. 0; 95% CI, 1.0 to 47) to be associated with prolonged hypoglycemia. No association between prolonged hypoglycemia and age, sex, beta blockers, angiotensin-converting enzyme inhibitors, oral hypoglycemic dose, or duration of treatment was identified. This study describes the potentially devastating effect of sulfonylurea-based oral hypoglycemic therapy in ESRD. Patients at greatest risk appear to be those with reduced intake, previous hypoglycemic episodes, and longer duration of diabetes. We describe the mechanisms for observed hypoglycemia and suggest that alternative drugs may be considered in this patient group.