In a hypertensive patient, what is renal function and how should it be evaluated, monitored, and managed?

Renal Function in Hypertensive Patients

Renal function refers to the kidney's ability to filter blood and excrete waste, measured primarily by glomerular filtration rate (GFR) and assessed through serum creatinine, with proteinuria serving as a critical marker of kidney damage—both of which must be routinely monitored in hypertensive patients as hypertension is both a cause and consequence of renal dysfunction. 1, 2

Definition and Key Components

Renal function encompasses several measurable parameters that reflect kidney health:

• Glomerular filtration rate (GFR) is the primary measure of kidney function, calculated using serum creatinine with the CKD-EPI formula to stage chronic kidney disease 1, 2
• Proteinuria/albuminuria indicates glomerular filtration barrier damage and should be quantified using 24-hour urine collection or spot urine protein-to-creatinine ratio 1
• Serum creatinine levels reflect waste product accumulation and inversely correlate with kidney function 3
• The combination of reduced eGFR and proteinuria indicates greater cardiovascular and renal event risk than either abnormality alone 2

Staging of Kidney Function

• Stage 2 CKD is defined as eGFR 60-89 ml/min/1.73m² 2
• Stage 3-4 CKD represents more advanced disease requiring aggressive blood pressure management 2
• Even mild reductions in GFR below 90 ml/min/1.73m² in hypertensive patients warrant closer monitoring 2

Pathophysiology in Hypertension

The relationship between hypertension and renal function is bidirectional and complex:

• Hypertension causes renal damage through progressive increases in intrarenal vascular resistance, leading to elevated renal vascular resistance, decreased renal blood flow, and sustained glomerular filtration rate with increased filtration fraction 4
• Renal dysfunction worsens hypertension through sodium retention, volume expansion, upregulation of the sympathetic nervous system, activation of the renin-angiotensin-aldosterone system, and endothelial dysfunction 5
• The alterations in renal hemodynamics are particularly accentuated in elderly hypertensive patients, indicating greater vulnerability of the aging kidney to hypertensive injury 6

Evaluation and Monitoring

Initial Assessment

• Calculate eGFR using the CKD-EPI formula from serum creatinine to establish baseline kidney function 1, 2
• Quantify proteinuria with 24-hour urine collection or spot urine protein-to-creatinine ratio 1
• Perform complete urinalysis with microscopy to differentiate active sediment (suggesting glomerulonephritis) from bland sediment (typical of hypertensive nephrosclerosis) 1
• Measure serum electrolytes, particularly potassium, as both hypokalemia from diuretics and hyperkalemia from renin-angiotensin-aldosterone system antagonists can occur 3

Ongoing Monitoring

• Recheck serum creatinine and potassium within 7-14 days after initiating or uptitrating ACE inhibitors or ARBs 1, 2
• Expect and tolerate up to 20-30% increase in serum creatinine after starting ACE inhibitor/ARB therapy, which reflects hemodynamic changes from reduced intraglomerular pressure rather than progressive kidney damage 1, 2
• Monitor proteinuria reduction as a treatment response marker, with a goal of reducing proteinuria by ≥30-50% from baseline 1
• Serial measurement of blood urea nitrogen relative to serum creatinine can indicate hypoperfusion when disproportionately elevated 3

Management Implications

Blood Pressure Targets

• Target blood pressure <130/80 mmHg in patients with chronic kidney disease and proteinuria, though evidence for targets below 120/80 mmHg remains mixed 3, 1, 2
• The MDRD trial showed significant reduction in end-stage renal disease with mean blood pressure below 120/80 mmHg in predominantly non-diabetic kidney disease, though other trials showed less benefit 3
• For stage 3-4 CKD, maintain BP <130/80 mmHg based on SPRINT trial data showing cardiovascular and mortality benefits 2

Pharmacological Approach

• Initiate ACE inhibitor (preferred) or ARB as first-line therapy at maximum tolerated doses in hypertensive patients with proteinuria, as these agents reduce intraglomerular pressure and slow progression to end-stage renal disease 1, 2
• Add thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) if blood pressure remains ≥140/90 mmHg on ACE inhibitor/ARB alone 1, 2
• Consider initial dual therapy with two antihypertensive medications if blood pressure is ≥150/90 mmHg to achieve more effective control 2
• Add mineralocorticoid receptor antagonist (spironolactone at low dose) for resistant hypertension despite three medications including a diuretic, with close potassium monitoring 2

Lifestyle Modifications

• Restrict dietary sodium to <2 g/day (ideally 1,200-2,300 mg/day) to enhance antihypertensive medication effectiveness and reduce proteinuria 1, 2
• Achieve weight loss if BMI >25 through caloric restriction 1
• Perform aerobic exercise ≥150 minutes/week of moderate-intensity activity 1, 2

Common Pitfalls

• Do not discontinue ACE inhibitor/ARB for creatinine increases up to 30%, as this reflects beneficial hemodynamic changes rather than harm 1, 2
• Monitor potassium closely when combining ACE inhibitors/ARBs with mineralocorticoid receptor antagonists, especially with reduced renal function 3, 2
• Recognize that rales are absent in most patients with chronic heart failure and elevated filling pressures, so their absence does not exclude volume overload 3
• Use 24-hour ambulatory BP monitoring or home BP measurements in CKD patients, as reduced or reverse dipping patterns, masked hypertension, and resistant hypertension are frequent and associated with poor prognosis 7