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A 54-year-old woman with type 2 diabetes presents for care. Her creatinine level has increased from 1.1 mg per deciliter (97 μmol per liter) 4 years ago to 3.1 mg per deciliter (274 μmol per liter) at the most recent measurement (estimated glomerular filtration rate, 26 ml per minute per 1.73 m 2 of body-surface area). Her urinary protein excretion is 2.8 g per 24 hours. Her blood pressure is 155/90 mm Hg, and the glycated hemoglobin level is 7.6 mg per deciliter. Her current medications include an oral hypoglycemic agent, an angiotensin-converting–enzyme inhibitor, a statin, and a thiazide diuretic. How should her case be managed? A 54-year-old woman presents with advanced diabetic kidney disease and proteinuria. How should her case be managed? Foreword This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage A 54-year-old woman with an 11-year history of type 2 diabetes presents for care. She was first noted to have proteinuria 4 years earlier; her serum creatinine level then was 1.1 mg per deciliter (97 μmol per liter). Her urinary protein excretion has progressively increased to 2.8 g per 24 hours, and her serum creatinine level to 3.1 mg per deciliter (274 μmol per liter). The estimated glomerular filtration rate (GFR) is 26 ml per minute per 1.73 m 2 of body-surface area. Her blood pressure is 155/90 mm Hg, and the glycated hemoglobin level is 7.6 mg per deciliter. . . .

In this trial, 947 patients with renal-artery stenosis were assigned to renal-artery stenting or medical therapy. At a median of 43 months, there was no significant between-group difference in the rate of a composite end point of adverse cardiovascular and renal events. Renal-artery stenosis, which is present in 1 to 5% of people with hypertension, 1 , 2 often occurs in combination with peripheral arterial or coronary artery disease. 3 , 4 Results of community-based screening suggest that the prevalence among persons older than 65 years of age may be as high as 7%. 5 Renal-artery stenosis may result in hypertension, ischemic nephropathy, and multiple long-term complications. 6 Uncontrolled studies performed in the 1990s suggested that renal-artery angioplasty or stenting resulted in significant reductions in systolic blood pressure 7 , 8 and in the stabilization of chronic kidney disease. 9 , 10 Subsequently, there were rapid increases in the rate of renal-artery . . .

Cigarette smoking causes cardiovascular disease and is associated with poor kidney function in individuals with diabetes mellitus and primary kidney diseases. However, the association of smoking on patients with atherosclerotic renal artery stenosis has not been studied. The current study utilized data from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL, NCT00081731) clinical trial to evaluate the effects of smoking on the risk of cardio-renal events and kidney function in this population. Baseline data showed that smokers (n = 277 out of 931) were significantly younger at enrollment than non-smokers (63.3±9.1 years vs 72.4±7.8 years; p<0.001). In addition, patients who smoke were also more likely to have bilateral renal artery stenoses and peripheral vascular disease (PVD). Longitudinal analysis showed that smokers experienced composite endpoint events (defined as first occurrence of: stroke; cardiovascular or renal death; myocardial infarction; hospitalization for congestive heart failure; permanent renal replacement; and progressive renal insufficiency defined as 30% reduction of GFR from baseline sustained for ≥ 60 days) at a substantially younger age compared to non-smokers (67.1±9.0 versus 76.1±7.9, p<0.001). Using linear regression and generalized linear modeling analysis controlled by age, sex, and ethnicity, smokers had significantly higher cystatin C levels (1.3±0.7 vs 1.2±0.9, p<0.01) whereas creatinine and estimated glomerular filtration rate (eGFR) were not different from non-smokers. From these data we conclude that smoking has a significant association with deleterious cardio-renal outcomes in patients with renovascular hypertension.

Preventing dialysis hypotension: A comparison of usual protective maneuvers. Intradialytic hypotension (IH) is a common adverse event. Currently, there are several commonly utilized therapies of IH, but they have not been compared directly in the same group of patients. We performed the present study in order to learn which of these techniques is most effective so that a rational approach to treating IH could then be formulated. A single-blinded, crossover study design of five different protocols was undertaken in 10 hemodialysis patients with a prior history of IH. Each patient first underwent one week (three dialyses) of standard dialysis (dialysate sodium 138 mEq/L). Then each patient was subjected to one week each (three dialyses) of the four test protocols, performed in random order in a blinded fashion. The specific protocols were as follows: high sodium dialysate, in which the patient was dialyzed using a dialysate sodium of 144 mEq/L; sodium modeling, during which the dialysate sodium declined from 152 to 140 mEq/L in the last half hour of dialysis; one hour of isolated ultrafiltration followed by three hours of isovolemic dialysis; and cool temperature dialysis in which the dialysate was cooled to 35°C. Weight loss in each of the five protocols was essentially identical, varying between 2.9 and 3 kg. There were significantly fewer hypotensive episodes per treatment in the sodium modeling, high sodium, and cool temperature protocols as compared with the standard protocol (P < 0.05). Ultrafiltration followed by dialysis was associated with a significantly greater number of hypotensive episodes per treatment than any of the three test protocols (P < 0.05). Similarly, the number of nursing interventions required for IH per treatment was significantly greater in the standard dialysis and in the isolated ultrafiltration protocols compared with sodium modeling and cool temperature protocols (P < 0.05). The number of hypotensive signs and symptoms per treatment was also significantly reduced during the sodium modeling and cool temperature protocols compared with the standard protocol (P < 0.004 and P < 0.02, respectively). Again, the isolated ultrafiltration protocol resulted in significantly more hypotensive symptoms and signs than the three test protocols (P < 0.005). Finally, the nadir mean arterial pressures were significantly lower in the standard and isolated ultrafiltration protocols when compared with the three test protocols (P < 0.05). The upright postdialysis blood pressure was best preserved in the sodium modeling and cool temperature protocols compared with the standard and isolated ultrafiltration protocols (P < 0.05). This study supports the use of sodium modeling as a first step in combating IH. Also effective were the use of cool-temperature dialysate and a high-sodium dialysate. All three test protocols were well tolerated. As applied in this study, isolated ultrafiltration followed by isovolemic dialysis was notably less effective in reducing IH.

Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown. CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of ≥60% with a 20 mm Hg systolic pressure gradient or ≥80% with no gradient necessary and (2) systolic hypertension of ≥155 mm Hg on ≥2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate. CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.

Intradialytic hypotension (IH) is a common adverse event. Currently, there are several commonly utilized therapies of IH, but they have not been compared directly in the same group of patients. We performed the present study in order to learn which of these techniques is most effective so that a rational approach to treating IH could then be formulated. A single-blinded, crossover study design of five different protocols was undertaken in 10 hemodialysis patients with a prior history of IH. Each patient first underwent one week (three dialyses) of standard dialysis (dialysate sodium 138 mEq/L). Then each patient was subjected to one week each (three dialyses) of the four test protocols, performed in random order in a blinded fashion. The specific protocols were as follows: high sodium dialysate, in which the patient was dialyzed using a dialysate sodium of 144 mEq/L; sodium modeling, during which the dialysate sodium declined from 152 to 140 mEq/L in the last half hour of dialysis; one hour of isolated ultrafiltration followed by three hours of isovolemic dialysis; and cool temperature dialysis in which the dialysate was cooled to 35 degrees C. Weight loss in each of the five protocols was essentially identical, varying between 2.9 and 3 kg. There were significantly fewer hypotensive episodes per treatment in the sodium modeling, high sodium, and cool temperature protocols as compared with the standard protocol (P < 0.05). Ultrafiltration followed by dialysis was associated with a significantly greater number of hypotensive episodes per treatment than any of the three test protocols (P < 0.05). Similarly, the number of nursing interventions required for IH per treatment was significantly greater in the standard dialysis and in the isolated ultrafiltration protocols compared with sodium modeling and cool temperature protocols (P < 0.05). The number of hypotensive signs and symptoms per treatment was also significantly reduced during the sodium modeling and cool temperature protocols compared with the standard protocol (P < 0.004 and P < 0.02, respectively). Again, the isolated ultrafiltration protocol resulted in significantly more hypotensive symptoms and signs than the three test protocols (P < 0.005). Finally, the nadir mean arterial pressures were significantly lower in the standard and isolated ultrafiltration protocols when compared with the three test protocols (P < 0.05). The upright postdialysis blood pressure was best preserved in the sodium modeling and cool temperature protocols compared with the standard and isolated ultrafiltration protocols (P < 0.05). This study supports the use of sodium modeling as a first step in combating IH. Also effective were the use of cool-temperature dialysate and a high-sodium dialysate. All three test protocols were well tolerated. As applied in this study, isolated ultrafiltration followed by isovolemic dialysis was notably less effective in reducing IH.

Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study. We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R. The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models. Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome. ClinicalTrials.gov, NCT00081731.