Does Nephrotic Syndrome (a collection of symptoms indicating kidney damage) cause Hypertension (high blood pressure)?

From the Guidelines

Nephrotic syndrome does not directly cause hypertension, but the two conditions can coexist, and hypertension may develop as a complication of impaired kidney function in patients with underlying kidney diseases or chronic kidney disease. Nephrotic syndrome is characterized by massive proteinuria (>3.5g/day), hypoalbuminemia, edema, and hyperlipidemia, which can lead to decreased effective circulating volume and low blood pressure rather than high blood pressure 1. However, some underlying kidney diseases that cause nephrotic syndrome, such as diabetic nephropathy, focal segmental glomerulosclerosis, or membranous nephropathy, may independently cause hypertension as they progress.

According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, hypertension is the most common comorbidity affecting patients with chronic kidney disease (CKD), and its presence can accelerate further kidney injury 1. The guideline recommends a blood pressure target of <130/80 mm Hg for all patients with CKD, including those with nephrotic syndrome, to prevent further kidney functional decline and reduce the risk of cardiovascular disease (CVD) and cerebrovascular events 1.

Key points to consider in the management of nephrotic syndrome and hypertension include:

• Reducing proteinuria with medications like ACE inhibitors or ARBs, which are preferred drugs for treatment of hypertension in patients with CKD and albuminuria 1
• Managing edema with diuretics, and sometimes using immunosuppressive therapy depending on the specific diagnosis
• Monitoring changes in eGFR and adjusting treatment accordingly
• Avoiding the combination of an ACE inhibitor and an ARB due to reported harms and lack of evidence supporting the combination therapy 1

In patients with diabetic or non-diabetic renal disease, the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) recommend lowering systolic blood pressure to <140 mmHg and pursuing values <130 mmHg when overt proteinuria is present, provided that changes in eGFR are monitored 1. Overall, the management of nephrotic syndrome and hypertension requires a comprehensive approach that addresses the underlying cause, reduces proteinuria, and prevents further kidney functional decline and cardiovascular complications.

From the Research

Nephrotic Syndrome and Hypertension

• Nephrotic syndrome is a kidney disorder characterized by heavy proteinuria, hypoalbuminemia, and edema, which can lead to various complications, including hypertension 2, 3.
• The pathophysiology of nephrotic syndrome involves the loss of protein in the urine, leading to hypoalbuminemia, which can cause fluid extravasation into the interstitial space, resulting in edema and potentially hypertension 4, 3.
• Studies have shown that patients with nephrotic syndrome are at risk of developing hypertension, and the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) is common in the management of these patients, particularly those with membranous nephropathy or focal segmental glomerulosclerosis 5.
• The incidence of ACEI/ARB prescription in patients with nephrotic syndrome has been shown to increase with higher baseline systolic blood pressure, suggesting a potential link between nephrotic syndrome and hypertension 5.

Management of Hypertension in Nephrotic Syndrome

• The management of hypertension in patients with nephrotic syndrome typically involves the use of diuretics, ACEIs, and ARBs, as well as lifestyle modifications such as sodium restriction and fluid restriction 2, 4.
• The choice of antihypertensive therapy in patients with nephrotic syndrome depends on various factors, including the underlying cause of the syndrome, the presence of other complications, and the patient's overall health status 6.
• Calcium antagonists may also be used in the management of hypertension in patients with nephrotic syndrome, particularly in those with isolated systolic hypertension or angina pectoris 6.

Complications of Nephrotic Syndrome

• Nephrotic syndrome can lead to various complications, including progressive kidney dysfunction, venous thrombosis, hyperlipidemia, and infection 2, 3.
• The risk of these complications can be reduced with appropriate management, including the use of antihypertensive therapy, diuretics, and immunosuppressive therapy, as well as lifestyle modifications such as sodium restriction and fluid restriction 2, 3.