Is early accelerated nephrosclerosis a stage in the perpetuating process of Chronic Kidney Disease (CKD)?

From the Guidelines

Yes, early accelerated nephrosclerosis is indeed a stage in the perpetuating process of chronic kidney disease (CKD). Nephrosclerosis refers to the hardening of small blood vessels in the kidneys, characterized by hyalinization of arterioles, thickening of vessel walls, and narrowing of the vessel lumen. When this process accelerates early in the disease course, it contributes significantly to the progressive nature of CKD. This pathological process reduces blood flow to nephrons, leading to ischemic damage, glomerulosclerosis, and tubular atrophy. The reduced perfusion triggers compensatory mechanisms including activation of the renin-angiotensin-aldosterone system (RAAS), which initially helps maintain glomerular filtration but eventually causes further damage through increased intraglomerular pressure and fibrosis.

Key Points to Consider

• Early detection and treatment of CKD can prevent or delay adverse outcomes, including kidney failure and cardiovascular disease 1.
• Management strategies targeting early accelerated nephrosclerosis include strict blood pressure control, preferably with RAAS inhibitors like ACE inhibitors or ARBs, to reduce intraglomerular pressure and fibrotic processes 1.
• The use of newer classes of glucose-lowering agents, such as sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists, has changed the therapeutic landscape for patients with diabetic kidney disease, offering opportunities to reduce the risk of progression and death 1.

Management Recommendations

• Strict blood pressure control (target <130/80 mmHg) is crucial in managing early accelerated nephrosclerosis, preferably with RAAS inhibitors like ACE inhibitors (e.g., lisinopril 10-40 mg daily) or ARBs (e.g., losartan 50-100 mg daily) 1.
• Early detection and treatment of CKD, including the use of markers like proteinuria and estimated glomerular filtration rate (eGFR), can help identify patients at risk and slow disease progression 1.
• An integrated approach to patient care with a multidisciplinary focus can help achieve the necessary shift in clinical care of patients with CKD, including those with diabetic kidney disease 1.

From the Research

Definition and Causes of Nephrosclerosis

• Nephrosclerosis is an umbrella term defining changes in all compartments of the kidney, caused by hypertension and aging 2.
• It is characterized by arteriolosclerosis and arteriolohyalinosis, leading to glomerular ischemic shrinking and sclerosis, along with glomerulomegaly and focal-segmental glomerulosclerosis (FSGS) 2.
• These lesions are accompanied by tubulointerstitial inflammation and fibrosis, which predict the decline of renal function 2.

Relationship between Nephrosclerosis and Chronic Kidney Disease (CKD)

• Nephrosclerosis is a major cause of renal insufficiency, particularly in blacks of African descent with a severe, early form of renovasculopathy and a rapid course to renal failure 2.
• Early accelerated nephrosclerosis may be a stage in the perpetuating process of CKD, as it can lead to a rapid decline in kidney function 3, 4.
• The progression of CKD can be influenced by various factors, including hypertension, diabetes, dyslipidemia, and obesity, which can damage the kidney directly and promote intrarenal atherogenesis 4.

Diagnosis and Treatment of Nephrosclerosis

• Early identification of kidney disease is crucial to protect kidney health and prevent disease progression 5.
• Serum creatinine and urine albumin can be used to estimate kidney function and assess for kidney and endothelial damage 5.
• Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may be effective in reducing the progression of CKD, although the evidence is limited and of low certainty 6.
• Other treatments, such as sodium glucose co-transporter-2 inhibitors, may also improve outcomes in patients with CKD 5.

Clinical Outcomes and Prognosis

• The clinical outcomes of patients with early accelerated nephrosclerosis are comparable to those without such a decline, when medical therapy only is continued 3.
• However, the progression of CKD can lead to a decline in renal function, increasing the risk of cardiovascular disease, and mortality 4, 2.
• Further research is needed to determine the effectiveness of ACEi and ARB in patients with stage 1 to 3 CKD who do not have diabetes mellitus (DM) 6.