Nitin Khosla

Predictors of Hyperkalemia Risk following Hypertension Control with Aldosterone Blockade

Background: Aldosterone antagonists have proven efficacy for management of resistant hypertension and proteinuria reduction; however, they are not widely used due to risk of hyperkalemia. This study assesses the risk factors for hyperkalemia in patients with chronic kidney disease (CKD) and resistant hypertension whose blood pressure (BP) is reduced to a guideline goal. Methods: This is a two-center study conducted in university-based hypertension clinics directed by clinical hypertension specialists. Forty-six patients with resistant hypertension and stages 2 or 3 CKD (mean estimated glomerular filtration rate (eGFR) 56.5 ± 16.2 ml/min/1.73 m2) were evaluated for safety and efficacy of aldosterone blockade added to preexisting BP-lowering regimens. All patients were on three mechanistically complementary antihypertensive agents including a diuretic and a renin-angiotensin system blocker. Patients were evaluated after a median of 45 treatment days. The primary endpoint was change in systolic BP. Secondary endpoints included change in serum potassium, creatinine, eGFR, diastolic BP and tolerability. Results: The mean age of the patients studied was 64.9 ± 10.7 years, all were obese and 86% had type 2 diabetes, with 82% being African-American. Addition of aldosterone antagonism yielded a further mean reduction in systolic BP of 14.7 ± 5.1 mm Hg (p = 0.001). Females with BMI >30 and those with a baseline systolic BP >160 mm Hg were more likely to have a greater BP reduction to aldosterone antagonism. In total, 39% of the patients had a >30% decrease in eGFR when the BP goal was achieved. The mean increase in serum potassium was 0.4 mEq/l above baseline (p = 0.001), with 17.3% manifesting hyperkalemia, i.e. serum potassium >5.5 mEq/l. Predictors of hyperkalemia included a baseline eGFR of ≤45 ml/min/1.73 m2 in whom serum potassium was >4.5 mEq/l on appropriately dosed diuretics. Contributing risks in this subgroup included a systolic BP reduction of >15 mm Hg associated with an eGFR fall of >30%. Conclusion: Aldosterone antagonism is effective and safe for achieving a BP goal among people with diabetic nephropathy when added to a triple antihypertensive regimen that includes a blocker of the renin-angiotensin system and an appropriately selected and dosed diuretic. Caution is advised when using aldosterone blockade for BP control in people with advanced stage 3 nephropathy with a serum potassium of >4.5 mEq/l for safety reasons.

Preexisting Chronic Kidney Disease: A Potential for Improved Outcomes from Acute Kidney Injury

BACKGROUND AND OBJECTIVES Acute kidney injury (AKI) is associated with adverse outcomes in critically ill patients. The influence of preexisting chronic kidney disease (CKD) on AKI outcomes is unclear. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We analyzed data from a prospective observational cohort study of AKI in critically ill patients who received nephrology consultation: the Program to Improve Care in Acute Renal Disease. In-hospital mortality rate, length of stay, and dialysis dependence were compared in patients with and without a prior history of CKD, defined by an elevated serum creatinine, proteinuria, and/or abnormal renal ultrasound within a year before hospitalization. We hypothesized that patients with AKI and prior history of CKD would have lower mortality rates, shorter lengths of stay, and higher rates of dialysis dependence than patients without prior history of CKD. RESULTS Patients with AKI and a prior history of CKD were older and underwent nephrology consultation earlier in the course of AKI. In-hospital mortality rate was lower (31 versus 40%, P = 0.04), and median intensive care unit length of stay was 4.6 d shorter (14.7 versus 19.3 d, P = 0.001) in patients with a prior history of CKD. Among dialyzed survivors, patients with prior CKD were also more likely to be dialysis dependent at hospital discharge. Differences in outcome were most evident in patients with lower severity of illness. CONCLUSIONS Among critically ill patients with AKI, those with prior CKD experience a lower mortality rate but are more likely to be dialysis dependent at hospital discharge. Future studies should determine optimal strategies for managing AKI with and without a prior history of CKD.

Lessons Learned from Recent Hypertension Trials about Kidney Disease

This article reviews BP trials with primary or secondary cardiovascular (CV) or renal end points. It focuses on how results of recent trials have influenced guidelines and clinical practice with specific reference to two issues: ( 1 ) Achievement of goal BP in patients with chronic kidney disease and ( 2 ) emerging data on the importance of decreasing proteinuria to prevent CV events and slow kidney disease progression. Each study is evaluated on its strengths and weaknesses as well as extrapolation of findings to the general population. The tenants of this article are that the baseline level of proteinuria and the magnitude of proteinuria reduction are important determinants of renal outcome in addition to lowering BP and should be consider in all future trials. Second, comparing trials of people with different stages of nephropathy and unknown or differing levels of proteinuria is limited in generalizing the CV or renal outcome to a more global population. As a preamble to this article, two observations are noteworthy: First, use of antihypertensive therapy in those with stage 3 nephropathy, i.e. , GFR of <60 ml/min, will not slow the rate of decline in kidney function to the same extent as in patients with normal kidney function (stage 1). Studies to address the aforementioned questions will not be performed, however, because of low event rates, relatively higher numbers of participants, and longer duration of follow-up, hence, higher cost than currently completed studies. Thus, we are faced with extrapolating from studies to clinical practice that may not be very appropriate. Second, observations from a number of clinical studies suggest that both risk for kidney disease progression as well as CV events may be inversely related to the level of kidney function and directly related to the amount of proteinuria (macroalbuminuria), defined as >300 mg/d of protein (1– …

The Kidney, Hypertension, and Remaining Challenges

There is an epidemic of chronic kidney disease in the Western world, with hypertension being the second most common cause. Blood pressure control rates, while improving, are still below 50% for the United States population. The following three challenges remain for the treatment of hypertension and associated prevention of end-stage kidney disease. First, a better understanding by the general medical community of how and in whom to use renin angiotensin aldosterone system blockers is needed. Second, the appropriate initiation of fixed-dose combination therapy to achieve blood-pressure goals needs to be clarified. Finally, the subgroup of patients with kidney disease needs more aggressive blood pressure lowering.

Emerging Therapies for Extracorporeal Support

Dialytic therapies have undergone major technological developments in the last decade and emerging techniques are promoted not only for acute kidney injury, but also for sepsis, acute decompensated heart failure, and acute and acute-on-chronic liver failure. New devices specifically target the pathophysiological mechanisms involved in these conditions. In septic shock and sepsis, high-volume hemofiltration, coupled plasma filtration adsorption, cascade hemofiltration and high permeability hemofiltration enhance removal of pro-inflammatory mediators, while in liver failure, Molecular Adsorbents recycling System (MARS®) and Prometheus® favor the elimination of albumin-bound toxins such as bilirubin. In acute decompensated heart failure, simplified ultrafiltration machines are used to reach negative fluid balance in a minimalist setting. In the context of limited resources and growing expansion in the availability of technologies, a critical assessment is required and the use of these devices needs to be put in perspective. This article reviews the mechanisms, advantages and limitations of these techniques along with the current evidence available regarding their influence on major clinical outcomes.

Contents Vol. 109, 2008

p37 First Joint Meeting of the French Society of Nephrology, the UK Renal Association and the Nephrology Section of the Royal Society of Medicine Royal Society of Medicine, London, February 28–29, 2008 Guest Editors Philip Mason (Oxford); Peter Mathieson (Bristol); Pierre Ronco (Paris) No. 3