Blockade of renin-angiotensin-aldosterone system in kidney and heart disease: how much do we need?

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in both cardiac and renal injury. Inhibition of RAAS with either an angiotensin converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB) provides both cardiac and renal protection, which is independent and additive to the benefit obtained from lowering blood pressure (BP). The combination of an ACE-I and an ARB should be used only for proteinuric renal disease and not for BP reduction. Patients with proteinuria >1 g/day despite optimal BP control with maximal dose of ACE-I or ARB monotherapy may benefit from a combination therapy. Inhibition of aldosterone with spironolactone or eplerenone provides survival advantage in patients with low LV ejection fraction and may also have antiproteinuric effects. Until further information is available, the routine combined use of all three inhibitors of the RAAS cannot be recommended.

Recent update in the management of hypertension.

Hypertension is still the leading cause of death worldwide. Hypertension increases not only the risk for progression of chronic kidney disease (CKD) but also for cardiovascular (CV) morbidity and mortality. For most patients it is the systolic blood pressure rather than the diastolic blood pressure that most strongly predicts adverse events. The optimal target for BP control for most hypertensive patients is < 140/90 mmHg, or < 130/80 mmHg for patients with diabetes and CKD. Certain lifestyle measures such as weight reduction, smoking cessation, restriction of dietary sodium intake, moderation of alcohol intake and an increase in physical activity can lower BP. Except for progression of proteinuric kidney disease and congestive heart failure (CHF), it is the achieved BP and not the class of agent that is most important in reducing morbid outcomes. If BP is more than 20/10 mmHg above the goal, therapy should be initiated with 2 drugs, one of which should be a thiazide-type diuretic. A strong consideration should be given to initiate antihypertensive therapy in patients with (RAAS) blockers, usually in concert with diuretics. Patients with proteinuria > 1 g/day despite optimal BP control with angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) monotherapy may benefit from a combination therapy.

Metabolic acidosis.

Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.

Secondary hyperparathyroidism and calcium phosphate control in a hemodialysis population.

AIM: To evaluate the prevalence of secondary hyperparathyroidism and calcium phosphate control in the hemodialysis Asian population. METHODS: We evaluated 36 patients at Tan Tock Seng Hospital in Singapore, who were receiving thrice weekly maintenance hemodialysis for at least 6 months. Patients with history of previous parathyroidectomy were excluded from the study. Patient's weight, length of dialysis per week, duration of dialysis, serum calcium, phosphate, albumin, bicarbonate, intact parathyroid hormone (iPTH), and single pool Kt/V were retrieved from patient's medical records. RESULTS: The mean length of weekly dialysis session and single pool Kt/V was 13.5 hours and 1.73 respectively. The majority of patients achieved the target range of serum phosphorus (67%), corrected calcium (58%) and calcium times phosphate (Ca ' P) product (81%). Only 25% of patients had levels of iPTH within the target range (150-300 pg/mL). Ninety four percent of the patients were on calcium-based phosphate binder and 42% on vitamin D therapy. A significant number of patients still fell out of the recommended guideline range for serum concentrations of phosphorus (11% of patients below lower target range, 22% of patients above upper target range), corrected calcium (3% below, 39% above), calcium-phosphorus product (19% above), and iPTH (58% below, 17% above). Thirty percent of the patients had levels of iPTH < 100 pg/mL. CONCLUSION: Compared to data reported from the USA, Europe and Japan, mean levels of phosphate, corrected calcium and Ca ' P product seem better controlled in this hemodialysis Asian population. However, more than half of the patients may have oversuppression of iPTH levels and a third of patients are at increased risk of developing a dynamic bone disease.

Approach to hyperkalemia.

Hyperkalemia is commonly found in hospitalized patients. Given the fact that untreated hyperkalemia is associated with high morbidity and mortality, it is critical to recognize and treat this disorder promptly. Patients at greatest risk for hyperkalemia include those with diabetes or impaired renal function, those with advanced age and those receiving drugs which interfere with renal potassium excretion. Hyperkalemia is likely to become an even more common clinical event, since ACE inhibitors, angiotensin-receptor blockers and aldosterone antagonists are increasingly being used in higher doses and in combination, in the belief that these measures provide additional cardiovascular and renal protection. The urgency of hyperkalemia treatment is dictated by change in electrocardiogram. Treatment of hyperkalemia includes calcium gluconate, insulin, beta agonists, sodium bicarbonate, cation exchange resin, diuretics and/or dialysis.

Approach to hypokalemia.

Hypokalemia is frequently encountered in clinical practice. It can be due to either potassium deficiency (inadequate potassium intake or excessive potassium loss) or to net potassium shifts from the extracellular to the intracellular compartment. Inadequate dietary intake of potassium alone rarely causes hypokalemia since kidney is able to lower potassium excretion below 15 mmol per day. Hypokalemia due to excessive potassium loss can be due to renal or extrarenal losses. It is not necessary to wait for a timed urine collection for potassium to determine the etiology of hypokalemia. Measurement of spot urine for potassium and creatinine as well as evaluation of acid-base status can be used as an initial step in the diagnosis of hypokalemia. Subsequent evaluations such as measurement of spot urinary chloride, blood pressure, serum aldosterone, renin and cortisol levels may be needed in certain circumstances.