Mesangial hypercellularity predicts antiproteinuric response to dual blockade of RAS in primary glomerulonephritis

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Very low protein diet supplemented with ketoanalogs improves blood pressure control in chronic kidney disease

Blood pressure (BP) is hardly controlled in chronic kidney disease (CKD). We compared the effect of very low protein diet (VLPD) supplemented with ketoanalogs of essential amino acids (0.35g/kg/day), low protein diet (LPD, 0.60g/kg/day), and free diet (FD) on BP in patients with CKD stages 4 and 5. Vegetable proteins were higher in VLPD (66%) than in LPD (48%). LPD was prescribed to 110 consecutive patients; after run-in, they were invited to start VLPD. Thirty subjects accepted; 57 decided to continue LPD; 23 refused either diet (FD group). At baseline, protein intake (g/kg/day) was 0.79±0.09 in VLPD, 0.78±0.11 in LPD, and 1.11±0.18 in FD (P<0.0001). After 6 months, protein intake was lower in VLPD than LPD and FD (0.54±0.11, 0.78±0.10, and 1.04±0.21g/kg/day, respectively; P<0.0001). BP diminished only in VLPD, from 143±19/84±10 to 128±16/78±7mm Hg (P<0.0001), despite reduction of antihypertensive drugs (from 2.6±1.1 to 1.8±1.2; P<0.001). Urinary urea excretion directly correlated with urinary sodium excretion, which diminished in VLPD (from 181±32 to 131±36mEq/day; P<0.001). At multiple regression analysis (R2=0.270, P<0.0001), BP results independently related to urinary sodium excretion (P=0.023) and VLPD prescription (P=0.003), but not to the level of protein intake. Thus, in moderate to advanced CKD, VLPD has an antihypertensive effect likely due to reduction of salt intake, type of proteins, and ketoanalogs supplementation, independent of actual protein intake

Combination therapy in hypertension: An update

Meticulous control of blood pressure is required in patients with hypertension to produce the maximum reduction in clinical cardiovascular end points, especially in patients with comorbidities like diabetes mellitus where more aggressive blood pressure lowering might be beneficial. Recent clinical trials suggest that the approach of using monotherapy for the control of hypertension is not likely to be successful in most patients. Combination therapy may be theoretically favored by the fact that multiple factors contribute to hypertension, and achieving control of blood pressure with single agent acting through one particular mechanism may not be possible. Regimens can either be fixed dose combinations or drugs added sequentially one after other. Combining the drugs makes them available in a convenient dosing format, lower the dose of individual component, thus, reducing the side effects and improving compliance. Classes of antihypertensive agents which have been commonly used are angiotensin receptor blockers, thiazide diuretics, beta and alpha blockers, calcium antagonists and angiotensin-converting enzyme inhibitors. Thiazide diuretics and calcium channel blockers are effective, as well as combinations that include renin-angiotensin-aldosterone system blockers, in reducing BP. The majority of currently available fixed-dose combinations are diuretic-based. Combinations may be individualized according to the presence of comorbidities like diabetes mellitus, chronic renal failure, heart failure, thyroid disorders and for special population groups like elderly and pregnant females

Ramipril and Risk of Hyperkalemia in Chronic Hemodialysis Patients

Angiotensin converting enzyme (ACE) inhibitors provide well known cardiorenal-protective benefits added to antihypertensive effects in chronic renal disease. These agents are underused in management of patients receiving hemodialysis (HD) because of common concern of hyperkalemia. However, few studies have investigated effect of renin angiotensin aldosterone system (RAAS) blockade on serum potassium in hemodialysis patients. We assessed the safety of ramipril in patients on maintenance HD. We enrolled 28 adult end stage renal disease (ESRD) patients treated by maintenance HD and prescribed them ramipril in doses of 1.25 to 5 mg per day. They underwent serum potassium concentration measurements before ramipril introduction and in 1 to 3 months afterwards. No significant increase in kalemia was found. Results of our study encourage the use of ACE inhibitors in chronically hemodialyzed patients, but close potassium monitoring is mandatory

Antiproteinuric Response to Dual Blockade of RAS in Primary Glomerulonephritis: Meta-Analysis and Meta-Regression

Background: In patients with primary glomerulonephritis (GN), antiproteinuric response to angiotensinconverting enzyme (ACE) inhibitors plus angiotensin receptor blockers (ARBs) versus either monotherapy is undefined because of the small size of studies and high heterogeneity of response. Study Design: Meta-analysis/metaregression. Setting & Population: Randomized clinical trials (RCTs). Selection Criteria for Studies: RCTs published from January 1996 to April 2007. Studies were excluded if information about levels of proteinuria was not available, patients had kidney disease other than primary GN, or if they had end-stage renal disease. Intervention: ACE inhibitor plus ARB versus monotherapy with 1 of these drug classes. Outcomes: Absolute changes in proteinuria (primary), blood pressure, serum potassium level, and glomerular filtration rate (GFR; secondary). Results: We found 13 RCTs including 425 patients with primary GN with proteinuria ranging from 0.8 to 7.9 g/d of protein and age from 25 to 60 years. Combination treatment decreased proteinuria by 0.60 g/d (95% confidence interval, 0.40 to 0.80) versus ACE-inhibitor monotherapy and 0.54 g/d (95% confidence interval, 0.30 to 0.78) versus ARB monotherapy. Baseline levels of proteinuria explained most between-study variability of the antiproteinuric response to combination therapy versus monotherapies. Systolic and diastolic blood pressure, GFR, age, and diagnosis of immunoglobulin A nephropathy did not modify antiproteinuric response. ACE-inhibitor plus ARB therapy did not change GFR, whereas it increased serum potassium levels (by 0.10 mEq/L versus ACE-inhibitor and 0.19 mEq/L versus ARB therapy) and decreased blood pressure. Limitations: Only published data are included. Conclusions: The antiproteinuric response to ACE-inhibitor plus ARB therapy versus either monotherapy is consistently greater and strictly related to baseline proteinuria, associated with only moderate increase in serum potassium levels, and not peculiar to immunoglobulin A nephropathy