From the Guidelines
Nephrotic syndrome secondary to diabetic kidney disease with normal creatinine should be managed with a multi-faceted approach focusing on blood pressure control, glycemic management, and proteinuria reduction, as recommended by the most recent guidelines 1.
Key Components of Management
- First-line treatment includes an angiotensin-converting enzyme inhibitor (ACE-I) such as lisinopril 10-40 mg daily or an angiotensin receptor blocker (ARB) like losartan 50-100 mg daily to reduce proteinuria and slow disease progression, as supported by studies 1.
- Optimal diabetes management is crucial, targeting HbA1c below 7% with appropriate medications, potentially including SGLT2 inhibitors like empagliflozin 10-25 mg daily or dapagliflozin 5-10 mg daily, which have shown renoprotective benefits independent of glucose control 1.
- Blood pressure should be maintained below 130/80 mmHg, with regular monitoring and adjustments as needed 1.
- Dietary modifications include sodium restriction (<2g/day), moderate protein restriction (0.8g/kg/day), and avoiding excessive protein intake, as recommended by guidelines 1.
Monitoring and Referral
- Regular monitoring of urine albumin-to-creatinine ratio, serum creatinine, electrolytes, and lipid profile is essential every 3-6 months to assess disease progression and response to treatment 1.
- Despite normal creatinine levels, significant kidney damage may be present, as creatinine typically rises only after substantial kidney function loss, highlighting the importance of early detection and management 1.
- Early nephrology referral is recommended for specialized care and to slow progression to more advanced kidney disease, particularly in cases with uncertainty about the etiology of kidney disease, difficult management issues, or advanced kidney disease 1.
From the Research
Nephrotic Syndrome Secondary to Diabetes with Normal Creatinine
- Nephrotic syndrome is a condition characterized by high levels of protein in the urine, low serum albumin, and edema, often associated with diabetic nephropathy 2.
- In patients with diabetic kidney disease, the definition of nephrotic syndrome has been evaluated, and the threshold levels for nephrotic-range proteinuria and albuminuria have been established as 3.5 g/d and 2.2 g/d, respectively 2.
- The renin-angiotensin-aldosterone system (RAAS) plays a central role in the pathogenesis and progression of diabetic renal disease, and RAAS inhibition with angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-II-receptor blockers (ARBs) is a standard therapeutic intervention in diabetic patients with chronic kidney disease (CKD) 3, 4, 5.
- Studies have shown that combined treatment with a mineralocorticoid receptor blocker (MRB) and an ACEI or ARB can further reduce albuminuria in diabetic nephropathy, but may increase the risk of hyperkalemia 4.
- In some cases, nephrotic syndrome can be reversible, as seen in a patient with Type 1 diabetes who presented with acute oliguric renal failure and nephrotic syndrome, but later recovered renal function after dialysis therapy 6.
Treatment and Management
- RAAS blockade is currently the best-documented treatment strategy to delay the progression of chronic proteinuric nephropathies, including diabetic nephropathy 3.
- ACE inhibitors and ARBs have been shown to be renoprotective in patients with diabetic nephropathy, and can prevent microalbuminuria in patients with type 2 diabetes who are hypertensive and normoalbuminuric 5.
- Mineralocorticoid receptor antagonists and direct renin inhibitors can be used as add-on treatments to standard therapy, including ACEIs or ARBs, to reduce albuminuria or proteinuria and retard the development of renal dysfunction 3, 4.