Overview of hypertension in acute and chronic kidney disease

INTRODUCTION — Hypertension is a frequent finding in both acute and chronic kidney disease, particularly with glomerular or vascular disorders [1]. The pathogenesis and preferred treatment of hypertension vary with the type of kidney disease and its duration. This topic will summarize the pathogenesis and treatment of hypertension in patients with acute and chronic kidney disease and then direct the reader, when necessary, to more detailed discussions in other topics.

PATHOGENESIS OF HYPERTENSION IN KIDNEY DISEASE — The pathogenesis of hypertension varies with the type of disease (eg, glomerular versus vascular) and with the duration of disease (acute versus chronic).

Acute glomerular disease — Patients with acute glomerular disease, such as poststreptococcal glomerulonephritis, tend to be volume expanded and edematous due to sodium retention [2]. As a result, the elevation in blood pressure is primarily due to fluid overload, as evidenced by suppression of the renin-angiotensin-aldosterone system and enhanced release of atrial natriuretic peptide [3]. Although these changes are most prominent with severe disease, the incidence of hypertension is increased even in patients with a normal serum creatinine concentration [4]. Both a familial predisposition to hypertension and subclinical volume expansion are thought to be important in this setting.

Experimental studies of the nephrotic syndrome or glomerulonephritis suggest that sodium retention in these disorders is due to increased reabsorption in the collecting tubules [5]. Two different abnormalities in collecting tubule function have been identified in glomerular disease, both of which could increase sodium reabsorption:

●Relative resistance to atrial natriuretic peptide due at least in part to more rapid degradation of the second messenger cyclic guanosine monophosphate (GMP) by the enzyme phosphodiesterase [4]. In an animal model of nephrotic syndrome, infusion of a phosphodiesterase inhibitor largely reverses this defect and restores the normal natriuretic response to volume expansion.

●Increased activity of the Na-K-ATPase pump in the cortical collecting tubule but not in other nephron segments [6]. This pump provides the energy for active sodium transport by pumping reabsorbed sodium out the cell into the peritubular capillary.

How these changes might be induced by the nephrotic syndrome or glomerulonephritis is not clear. They are not likely to be mediated by aldosterone, the secretion of which is reduced by volume expansion-mediated reductions in plasma renin activity [3].

Acute vascular disease — Hypertension is also common in acute vascular diseases, such as vasculitis or scleroderma renal crisis. In these settings, the elevation in blood pressure results from ischemia-induced activation of the renin-angiotensin system rather than volume expansion [2]. This difference in mechanism between glomerular and vascular disease may be of therapeutic importance. (See 'Treatment of hypertension in acute glomerular or vascular disease' below.)

Chronic kidney disease — Hypertension is present in approximately 80 to 85 percent of patients with CKD [7]. The prevalence of hypertension is even elevated in patients with kidney damage and a normal glomerular filtration rate (GFR) and increases further as the GFR falls. Data from the Modification of Diet in Renal Disease Study, for example, showed that the prevalence of hypertension rose progressively from 65 to 95 percent as the GFR fell from 85 to 15 mL/min per 1.73 m² [8]. As in patients without kidney disease, the prevalence of hypertension is also higher in patients with higher body weight and in Black patients. (See "Overweight, obesity, and weight reduction in hypertension", section on 'Effects of adiposity on blood pressure' and "Burden of hypertension in Black individuals".)

A variety of factors can contribute to the increased prevalence of hypertension in patients with CKD:

●Sodium retention is generally of primary importance, even though the degree of extracellular volume expansion may be insufficient to induce edema.

●Increased activity of the renin-angiotensin system is often responsible for at least part of the hypertension that persists after the restoration of euvolemia, particularly in patients with vascular disease since kidney ischemia is a potent stimulus of renin secretion. Regional ischemia induced by scarring may also play a role.

●Hypertension can be a causative (eg, hypertensive nephrosclerosis) or contributory factor in the development of kidney disease.

●Hypertension may result from enhanced activity of the sympathetic nervous system [9]. The afferent signal may arise in part within the failing kidneys since it is not seen in patients who have undergone bilateral nephrectomy.

●Secondary hyperparathyroidism raises the intracellular calcium concentration, which can lead to vasoconstriction and hypertension [10]. Lowering parathyroid hormone secretion by the chronic administration of an active vitamin D analog can reduce both intracellular calcium and systemic blood pressure.

●Treatment of anemia in CKD with erythropoietin or HIF stabilizers may increase blood pressure, an effect that is in part related to the degree of elevation in the hematocrit. (See "Hypertension associated with erythropoiesis-stimulating agents (ESAs) in patients with chronic kidney disease", section on 'Pathogenesis'.)

●Impaired nitric oxide synthesis and endothelium-mediated vasodilatation has been demonstrated in patients with uremia [11]. Although the mechanisms are unclear, potential explanations include reduced nitric oxide availability due to a state of increased oxidative stress or cofactor deficiency-induced uncoupling of nitric oxide synthase.

In addition to the factors that can raise mean arterial pressure, two other factors may be important:

●Patients with end-stage kidney disease (ESKD) are more likely to have an increase in central pulse pressure and isolated systolic hypertension [12]. Why this occurs is incompletely understood, but increased aortic stiffness probably plays an important role.

●Patients with CKD may not demonstrate the normal nocturnal decline in blood pressure (such patients are called "nondippers"), a possible risk factor for hypertensive complications [13]. (See "Out-of-office blood pressure measurement: Ambulatory and self-measured blood pressure monitoring".)

TREATMENT OF HYPERTENSION IN ACUTE GLOMERULAR OR VASCULAR DISEASE — In view of the differences in pathogenesis, the mechanism and treatment of hypertension vary in patients with acute glomerular and vascular disease.

We prefer initial therapy with diuretics (particularly loop diuretics in patients with reduced glomerular filtration rates [GFRs]) to treat hypertension in patients with acute glomerular disease and edema since diuretics will also treat the hypervolemia and associated edema. If the hypertension persists, angiotensin-converting enzyme (ACE) inhibitors may be effective, even in the low-renin hypertension often associated with acute glomerulonephritis [14]. This response may reflect activation of tissue renin-angiotensin systems, such as that in the kidney, vascular endothelium, and adrenal gland. (See "Renin-angiotensin system inhibition in the treatment of hypertension".)

In comparison with acute glomerulonephritis, we prefer ACE inhibitors as initial antihypertensive therapy in patients with acute vascular diseases since kidney ischemia leads to activation of the renin-angiotensin system. Strong data support this approach in patients with scleroderma renal crisis, and we prefer angiotensin inhibition in polyarteritis nodosa and other vasculitides, as well. (See "Kidney disease in systemic sclerosis (scleroderma), including scleroderma renal crisis", section on 'Treatment' and "Treatment and prognosis of polyarteritis nodosa", section on 'Hypertension'.)

TREATMENT OF HYPERTENSION IN CHRONIC KIDNEY DISEASE — Treatment of even mild or stage 1 hypertension is important in patients with CKD to protect against both progressive kidney function loss and cardiovascular disease, the incidence of which is increased with mild to moderate stages 1 to 3 CKD. (See "Antihypertensive therapy and progression of nondiabetic chronic kidney disease in adults" and "Chronic kidney disease and coronary heart disease", section on 'Blood pressure control'.)

Our approach to managing hypertension in patients with CKD is presented in other topics:

●Goal blood pressure – Goal blood pressure in patients with diabetic and nondiabetic CKD is similar to that in other patients at high cardiovascular risk (table 1) (see "Goal blood pressure in adults with hypertension", section on 'Patients with chronic kidney disease' and "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus').

●Method of blood pressure measurement – Acceptable methods of blood pressure measurement to determine if a patient with CKD is at goal include (see "Blood pressure measurement in the diagnosis and management of hypertension in adults"):

•Standardized office blood pressure measurement (table 2)

•Automated office blood pressure monitoring (AOBPM)

•Self-measured (ie, home) blood pressure measurement

•24-hour ambulatory blood pressure measurement

Casual office blood pressure should not be used to determine if a patient is at goal [15].

●Sodium restriction – Sodium restriction enhances the effect of many antihypertensive drugs; this is also true in patients with CKD [16,17] (see "Salt intake and hypertension").

●Pharmacologic therapy – The choice of antihypertensive medications in patients with CKD is similar to that in patients without CKD (algorithm 1) (see "Choice of drug therapy in primary (essential) hypertension", section on 'Patients with CKD').

When diuretics are used in the treatment regimen, the choice of agent is guided in part by the level of kidney function impairment (see "Thiazides versus loop diuretics in the treatment of hypertension").

Hypervolemia, which contributes to hypertension, is generally more difficult to treat in patients with CKD. Thus, higher doses of diuretics are typically needed (table 3) (see "Causes and treatment of refractory edema in adults").

●Patients receiving dialysis – The treatment of hypertension in patients receiving dialysis is different than that in other patients with CKD (see "Hypertension in patients on dialysis").

SUMMARY AND RECOMMENDATIONS

●Pathogenesis of hypertension in kidney disease

•Acute glomerular disease – Patients with acute glomerular disease tend to be volume expanded and edematous due to sodium retention. As a result, the elevation in blood pressure is thought to be primarily due to fluid overload, as evidenced by suppression of the renin-angiotensin-aldosterone system and enhanced release of atrial natriuretic peptide. (See 'Acute glomerular disease' above.)

•Acute vascular disease – In acute vascular diseases, such as vasculitis or scleroderma, the elevation in blood pressure results from ischemia-induced activation of the renin-angiotensin system rather than volume expansion. (See 'Acute vascular disease' above.)

•Chronic kidney disease (CKD) – In patients with CKD, hypertension is likely due to a combination of factors including sodium retention, increased activity of the renin-angiotensin system, and enhanced activity of the sympathetic nervous system. (See 'Chronic kidney disease' above.)

●Treatment of hypertension in acute kidney disease – The hypertension in acute glomerular disease with edema typically resolves after fluid removal with diuretics or, if necessary, dialysis. By comparison, lowering angiotensin II formation with an angiotensin-converting enzyme (ACE) inhibitor is effective in many patients with vasculitis or scleroderma. (See 'Treatment of hypertension in acute glomerular or vascular disease' above.)

●Treatment of hypertension in CKD – Management of hypertension in CKD, including goal blood pressure, method of measurement, sodium restriction, and pharmacologic therapy are presented in other topics. (See 'Treatment of hypertension in chronic kidney disease' above and "Goal blood pressure in adults with hypertension", section on 'Patients with chronic kidney disease' and "Blood pressure measurement in the diagnosis and management of hypertension in adults" and "Salt intake and hypertension" and "Choice of drug therapy in primary (essential) hypertension".)