How should a patient with Type 2 Diabetes Mellitus, newly diagnosed hypertension, and a history of generalized body swelling, now presenting with worsening swelling, impaired renal function, hyperkalemia, and suspected pneumonia, be managed?

Management of Type 2 Diabetes with Nephrotic Syndrome, AKI on CKD, and Hyperkalemia

This patient requires immediate escalation of loop diuretic therapy, strict avoidance of ACE inhibitors/ARBs until renal function stabilizes, addition of an SGLT2 inhibitor for both glycemic control and hyperkalemia management, and treatment of suspected pneumonia with azithromycin while addressing volume overload aggressively.

Immediate Priorities (First 48-72 Hours)

Diuretic Management for Volume Overload

• Increase furosemide from 40 mg IV TID to at least 80-100 mg IV TID (double to 2.5× the current dose), as the current regimen is inadequate given the massive volume overload with bilateral pleural effusions, ascites, and anasarca 1, 2.
• Loop diuretics maintain efficacy even with severe renal impairment (GFR <30 mL/min, estimated ~25 mL/min in this patient based on creatinine 3.69 mg/dL), whereas thiazides become completely ineffective at this level of renal dysfunction 2, 3.
• If inadequate diuresis occurs within 24-48 hours despite dose escalation, switch to bumetanide or torsemide due to superior oral bioavailability and more predictable absorption in the setting of bowel edema 1, 2.
• For persistent diuretic resistance, add metolazone 2.5-5 mg daily (or chlorthalidone) for sequential nephron blockade, monitoring closely for electrolyte derangements 2.

Critical: Do NOT Start ACE Inhibitors or ARBs Yet

• ACE inhibitors/ARBs are contraindicated in the acute phase of nephrotic syndrome with AKI, particularly when minimal change disease cannot be excluded 4.
• The abrupt onset of nephrotic syndrome (generalized body swelling developing over 1 week, now recurring) raises concern for minimal change disease, where ACE inhibitors/ARBs can precipitate further acute kidney injury 4.
• Delay ACE inhibitor/ARB initiation until: (1) serum creatinine stabilizes or improves for at least 5-7 consecutive days, (2) volume status is optimized, and (3) minimal change disease is ruled out by renal biopsy results or clinical course 4, 3.

Hyperkalemia Management

• The potassium level of 6.0 mEq/L (now 4.87 mEq/L) requires ongoing vigilance, especially with declining renal function 5.
• Add an SGLT2 inhibitor (dapagliflozin 10 mg daily or empagliflozin 10 mg daily) once volume status improves slightly, as SGLT2 inhibitors reduce the risk of serious hyperkalemia by 16% (hazard ratio 0.84) and allow safer future introduction of RAAS inhibitors 1.
• SGLT2 inhibitors provide the additional benefits of: improved glycemic control (HbA1c 9.0% indicates poor control), reduced proteinuria, slowed CKD progression, and cardiovascular protection 1.
• Avoid potassium-containing salt substitutes and potassium supplementation 5.
• Monitor serum potassium within 1 week of any medication changes and regularly thereafter 5.

Glycemic Control Optimization

Insulin Management

• Continue the modified insulin sliding scale and regular insulin shifting therapy (10 IU RI with D40% QID) as currently prescribed for acute glycemic management.
• Target HbA1c <7% long-term to slow progression of diabetic kidney disease, as aggressive glycemic control significantly reduces microvascular complications including nephropathy 1, 6.
• Once acute illness resolves, transition to a basal-bolus insulin regimen with dose adjustments for renal impairment (insulin requirements typically decrease as GFR declines).

SGLT2 Inhibitor Addition

• Initiate dapagliflozin 10 mg daily or empagliflozin 10 mg daily once the patient is no longer critically volume overloaded (after 48-72 hours of aggressive diuresis) 1.
• SGLT2 inhibitors are safe and effective even with GFR 20-30 mL/min, providing renoprotection and reducing hyperkalemia risk 1.
• These agents may allow for reduced loop diuretic doses over time and facilitate future RAAS inhibitor introduction 1.

Infection Management

Pneumonia Treatment

• Continue azithromycin as ordered for suspected right lower lobe pneumonia (CXR showing right lower lung zone patchy opacity, dry cough for 1 week) [@case presentation@].
• Monitor respiratory status closely given bilateral pleural effusions and SpO2 87% on room air.
• Maintain supplemental oxygen to keep SpO2 >92%.

Blood Pressure Management (Acute Phase)

Avoid RAAS Inhibitors Initially

• Current BP 125/80 mmHg is acceptable during acute stabilization; aggressive BP lowering is not indicated in the setting of AKI 4.
• Use calcium channel blockers (amlodipine 5-10 mg daily) if additional BP control is needed during the acute phase, as they do not worsen renal function in nephrotic syndrome with AKI 4.
• Target BP <130/80 mmHg once volume status is optimized, but avoid aggressive lowering that could compromise renal perfusion in the setting of AKI 1.

Transition to Long-Term Management (After Stabilization)

Introduction of ACE Inhibitors/ARBs

• After renal function stabilizes (stable creatinine for 5-7 days), initiate low-dose ACE inhibitor (enalapril 2.5 mg daily) or ARB (losartan 25 mg daily) 4, 3.
• Losartan has the broadest evidence base across different causes of nephrotic syndrome, including diabetic nephropathy 4.
• Titrate gradually to maximum tolerated dose (losartan 100 mg daily) for optimal renoprotection, not just BP control 4, 3.
• Monitor serum creatinine and potassium 1-2 weeks after initiation; an initial creatinine increase up to 30% is acceptable and usually returns to baseline 3.
• Discontinue if creatinine continues to rise >30% or refractory hyperkalemia develops 3.

Long-Term Blood Pressure Target

• Target systolic BP <120 mmHg using standardized office measurement to slow CKD progression and reduce cardiovascular risk 4, 3.
• Target proteinuria reduction to <1 g/day, not just BP control 4.
• Combination therapy will likely be necessary: ACE inhibitor/ARB + calcium channel blocker + loop diuretic 3.

Additional Renoprotective Measures

• Sodium restriction to <2.0 g/day (<90 mmol/day) is essential for both BP control and reducing proteinuria 3, 4.
• Initiate statin therapy (atorvastatin 40-80 mg daily) for cardiovascular risk reduction and potential reduction in proteinuria 1, 3.
• Avoid nephrotoxic medications, particularly NSAIDs, which reduce diuretic efficacy and can precipitate acute kidney injury 2, 3.

Monitoring and Nephrology Consultation

Essential Monitoring

• Daily weights, strict intake/output monitoring.
• Serum creatinine, BUN, electrolytes (Na, K, Cl, Ca) every 1-2 days initially, then weekly 5.
• Random blood sugar QID as ordered, with adjustment of insulin regimen.
• Repeat 24-hour urine protein after stabilization to assess response to therapy.

Nephrology Referral

• Urgent nephrology consultation is mandatory given GFR <30 mL/min (Stage 3b-4 CKD), massive proteinuria (2016 mg/24h), and AKI on CKD 3.
• Renal biopsy may be indicated to differentiate diabetic nephropathy from other causes (minimal change disease, membranous nephropathy, or other glomerulopathies), especially given the relatively short duration of diabetes (6 years) and abrupt onset of nephrotic syndrome 4, 7.
• Begin discussions about renal replacement therapy options (hemodialysis, peritoneal dialysis, transplantation) as preparation should begin when GFR <30 mL/min 3.

Critical Pitfalls to Avoid

• Do not start ACE inhibitors/ARBs during acute nephrotic syndrome with AKI—this can worsen renal function, particularly if minimal change disease is present 4.
• Do not use thiazide diuretics as monotherapy—they are ineffective at GFR <40 mL/min and should only be added to loop diuretics for sequential nephron blockade 2, 3.
• Do not underdose loop diuretics—inadequate diuresis perpetuates volume overload and worsens outcomes; use at least 2× the home dose intravenously 1, 2.
• Do not add spironolactone given hyperkalemia (K 6.0 mEq/L) and severe renal impairment (GFR ~25 mL/min)—risk of life-threatening hyperkalemia is prohibitive 5.
• Do not delay SGLT2 inhibitor initiation—these agents reduce hyperkalemia risk, improve glycemic control, and provide renoprotection even at low GFR 1.