Predicting the risks of kidney failure and death in adults with moderate to severe chronic kidney disease: multinational, longitudinal, population based, cohort study.

OBJECTIVE: To train and test a super learner strategy for risk prediction of kidney failure and mortality in people with incident moderate to severe chronic kidney disease (stage G3b to G4). DESIGN: Multinational, longitudinal, population based, cohort study. SETTINGS: Linked population health data from Canada (training and temporal testing), and Denmark and Scotland (geographical testing). PARTICIPANTS: People with newly recorded chronic kidney disease at stage G3b-G4, estimated glomerular filtration rate (eGFR) 15-44 mL/min/1.73 m2. MODELLING: The super learner algorithm selected the best performing regression models or machine learning algorithms (learners) based on their ability to predict kidney failure and mortality with minimised cross-validated prediction error (Brier score, the lower the better). Prespecified learners included age, sex, eGFR, albuminuria, with or without diabetes, and cardiovascular disease. The index of prediction accuracy, a measure of calibration and discrimination calculated from the Brier score (the higher the better) was used to compare KDpredict with the benchmark, kidney failure risk equation, which does not account for the competing risk of death, and to evaluate the performance of KDpredict mortality models. RESULTS: 67 942 Canadians, 17 528 Danish, and 7740 Scottish residents with chronic kidney disease at stage G3b to G4 were included (median age 77-80 years; median eGFR 39 mL/min/1.73 m2). Median follow-up times were five to six years in all cohorts. Rates were 0.8-1.1 per 100 person years for kidney failure and 10-12 per 100 person years for death. KDpredict was more accurate than kidney failure risk equation in prediction of kidney failure risk: five year index of prediction accuracy 27.8% (95% confidence interval 25.2% to 30.6%) versus 18.1% (15.7% to 20.4%) in Denmark and 30.5% (27.8% to 33.5%) versus 14.2% (12.0% to 16.5%) in Scotland. Predictions from kidney failure risk equation and KDpredict differed substantially, potentially leading to diverging treatment decisions. An 80-year-old man with an eGFR of 30 mL/min/1.73 m2 and an albumin-to-creatinine ratio of 100 mg/g (11 mg/mmol) would receive a five year kidney failure risk prediction of 10% from kidney failure risk equation (above the current nephrology referral threshold of 5%). The same man would receive five year risk predictions of 2% for kidney failure and 57% for mortality from KDpredict. Individual risk predictions from KDpredict with four or six variables were accurate for both outcomes. The KDpredict models retrained using older data provided accurate predictions when tested in temporally distinct, more recent data. CONCLUSIONS: KDpredict could be incorporated into electronic medical records or accessed online to accurately predict the risks of kidney failure and death in people with moderate to severe CKD. The KDpredict learning strategy is designed to be adapted to local needs and regularly revised over time to account for changes in the underlying health system and care processes.

Antihypertensive medications and the risk of kidney stones in older adults: a retrospective cohort study.

Antihypertensives are widely prescribed and could influence kidney stone risk by altering urinary calcium excretion. However, the impact of different classes of antihypertensives on kidney stone risk is unknown. To assess this impact, we conducted a retrospective, population-based cohort study using linked health administrative databases. Individuals aged >65 years who initiated one of the four antihypertensive classes (that is, angiotensin-converting enzyme inhibitors (ACEis)/angiotensin receptor blockers (ARBs), beta-blockers, calcium channel blockers or thiazide diuretics) were included. The participants were followed for the occurrence of a kidney stone event while maintaining continuous usage on their drug class. The association between antihypertensive class and outcome was estimated by Cox regression. Of the 542 581 people included, we observed 4533 kidney stone events (0.83%) over a median follow-up of 368 days (365-729). Compared with beta-blockers, thiazides were associated with a lower risk of kidney stones (hazard ratio (HR) 0.76; 95% confidence interval (CI) 0.68-0.84), ACEis/ARBs with a borderline decreased risk (HR 0.90; 95% CI 0.83-0.98) and calcium channel blockers with a comparable risk (HR 1.02; 95% CI 0.92-1.13). When the risk of requiring an intervention for a kidney stone was examined, the results were consistent with the primary analysis; however, the protective effect of ACEis/ARBs was eliminated (HR 0.96; 95% CI 0.87-1.06). In conclusion, relative to beta-blockers, thiazide diuretics were associated with a decreased risk of kidney stone formation in adults aged >65 years, whereas ACEis/ARBs and calcium channel blockers had a comparable risk of presenting with a kidney stone.

Urine creatinine excretion and clinical outcomes in CKD.

BACKGROUND AND OBJECTIVES: Twenty-four-hour urine creatinine excretion is a reliable approximation of muscle mass. Whether changes in urine creatinine predict clinical outcomes in persons with CKD is unknown. This work studied the relationship between urine creatinine and patient and renal survival in people with CKD not requiring renal replacement therapy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This longitudinal cohort study included incident stages 3-5 CKD patients referred to the renal clinic at the University Federico II in Naples between January of 1995 and December of 2005. Clinical data and urine creatinine were updated at each visit. Main outcomes were all-cause mortality and kidney failure requiring dialysis. RESULTS: This study enrolled 525 individuals and followed them for a median of 6 years (range of 4 months to 15 years). Urine creatinine excretion declined by 16 mg/d per year (95% confidence interval, 14 to 19) in participants with CKD stages 3a, 3b, and 4, and it remained stable in participants with stage 5 CKD. Per each 20 mg/d decline in urine creatinine, mortality increased by 3% (adjusted hazard ratio, 1.03; 95% confidence interval, 1.01 to 1.05), and the risk of initiating dialysis increased by 2% (adjusted hazard ratio, 1.02; 95% confidence interval, 1.01 to 1.03). These associations were independent of body mass index and GFR. CONCLUSIONS: In persons with CKD stages 3 and 4, urine creatinine declines at a rate of 16 mg/d per year. Lower urine creatinine excretion predicts greater risk of kidney failure and patient mortality.

Temporal risk profile for infectious and noninfectious complications of hemodialysis access.

Vascular access complications are a major cause of morbidity in patients undergoing hemodialysis, and determining how the risks of different complications vary over the life of an access may benefit the design of prevention strategies. We used data from the Dialysis Outcomes and Practice Patterns Study (DOPPS) to assess the temporal profiles of risks for infectious and noninfectious complications of fistulas, grafts, and tunneled catheters in incident hemodialysis patients. We used longitudinal data to model time from access placement or successful treatment of a previous complication to subsequent complication and considered multiple accesses per patient and repeated access complications using baseline and time-varying covariates to obtain adjusted estimates. Of the 7769 incident patients identified, 7140 received at least one permanent access. During a median follow-up of 14 months (interquartile range, 7-22 months), 10,452 noninfectious and 1131 infectious events (including 551 hospitalizations for sepsis) occurred in 112,085 patient-months. The hazards for both complication types declined over time in all access types: They were 5-10 times greater in the first 3-6 months than in later periods after access placement or a remedial access-related procedure. The hazards declined more quickly with fistulas than with grafts and catheters (P<0.001; Weibull regression). These data indicate that risks for noninfectious and infectious complications of the hemodialysis access decline over time with all access types and suggest that prevention strategies should target the first 6 months after access placement or a remedial access-related procedure.