What is the appropriate management for a 71‑year‑old man with stage 3a chronic kidney disease (eGFR ≈ 56 mL/min), type 2 diabetes mellitus (A1C 8.4 %), chronic heart failure, chronic respiratory failure, mild thrombocytopenia (platelet count 140 × 10⁹/L) and mild hyperbilirubinemia (total bilirubin 1.6 mg/dL)?

Management of Mild Thrombocytopenia and Hyperbilirubinemia in a Complex CKD Patient

The mild thrombocytopenia (140 × 10⁹/L) and hyperbilirubinemia (1.6 mg/dL) require investigation but should not delay optimization of this patient's diabetes and CKD management with SGLT2 inhibitors, RAS blockade, and improved glycemic control—the priority is preventing cardiovascular events and kidney failure, which pose far greater immediate mortality risk than these borderline laboratory abnormalities. 1

Immediate Priorities: Address Modifiable Cardiovascular and Kidney Risk

Optimize Diabetes Management (A1C 8.4%)

• Initiate an SGLT2 inhibitor immediately (empagliflozin, dapagliflozin, or canagliflozin) as this patient has type 2 diabetes with CKD stage 3a (eGFR 56 mL/min/1.73 m²), which meets the strongest (1A) recommendation for SGLT2i therapy to reduce cardiovascular events, heart failure hospitalization, and CKD progression. 1

• Continue SGLT2i even if eGFR declines below 20 mL/min/1.73 m² once initiated, unless intolerance or dialysis occurs. 1

• Add or optimize a GLP-1 receptor agonist (semaglutide, dulaglutide, or liraglutide) if glycemic targets are not met with SGLT2i, prioritizing agents with proven cardiovascular benefits. 1

• Avoid or discontinue metformin if eGFR falls below 45 mL/min/1.73 m²; at eGFR 56, metformin can be continued at reduced dose (≤1000 mg daily) but should be stopped if kidney function declines further. 2, 3

• Target A1C of 7.0–8.0% in this 71-year-old with multiple comorbidities and chronic heart/respiratory failure, balancing microvascular benefits against hypoglycemia risk. 1

Maximize RAS Blockade

• Initiate or uptitrate an ACE inhibitor or ARB to the maximum tolerated dose if the patient has albuminuria or hypertension, as this slows CKD progression and reduces cardiovascular events. 1

• Continue RAS inhibition even if eGFR falls below 30 mL/min/1.73 m² unless symptomatic hypotension, refractory hyperkalemia, or uremic symptoms develop. 1, 4

• Accept up to 30% rise in serum creatinine within 4 weeks of RAS inhibitor initiation or dose increase—this reflects hemodynamic adaptation, not kidney injury. 1, 4

• Check serum creatinine and potassium 2–4 weeks after starting or increasing RAS inhibitor, then monitor potassium every 2–4 weeks initially. 1, 4

Consider Nonsteroidal MRA

• Add finerenone (10 mg daily for eGFR 25–59 mL/min/1.73 m²) if albuminuria persists despite maximum-tolerated RAS inhibitor and SGLT2i, provided serum potassium is ≤4.8 mmol/L. 1

• Monitor potassium at 1 month, then every 4 months; hold finerenone if K⁺ >5.5 mmol/L and manage hyperkalemia with dietary restriction or potassium binders rather than stopping RAS blockade. 1, 4

Investigate the Thrombocytopenia and Hyperbilirubinemia

Thrombocytopenia (140 × 10⁹/L)

• This platelet count is at the lower limit of normal and does not contraindicate aspirin or other antiplatelet therapy if indicated for secondary cardiovascular prevention. 1

• Review medications for drug-induced thrombocytopenia (thiazides, loop diuretics, heparin, antibiotics, NSAIDs).

• Obtain a complete blood count with peripheral smear to exclude pseudothrombocytopenia, myelodysplasia, or other hematologic disorders.

• Check for chronic liver disease (see below) and consider bone marrow suppression from uremia if thrombocytopenia worsens.

• Aspirin for secondary prevention should be continued lifelong in patients with established cardiovascular disease, balancing bleeding risk against thrombotic risk; primary prevention with aspirin may be considered in high-risk individuals but weigh against bleeding risk, especially with low GFR. 1

Hyperbilirubinemia (1.6 mg/dL)

• Fractionate bilirubin (direct vs. indirect) to distinguish hepatocellular injury, cholestasis, or hemolysis.

• Check liver enzymes (ALT, AST, alkaline phosphatase, GGT), albumin, and INR to assess hepatic synthetic function and exclude chronic liver disease.

• Review medications for hepatotoxicity (statins, fibrates, azole antifungals, antibiotics).

• Consider right upper quadrant ultrasound if cholestatic pattern or if hepatomegaly/splenomegaly is present on examination.

• Evaluate for hemolysis (reticulocyte count, haptoglobin, LDH) if indirect hyperbilirubinemia predominates.

• Recognize that mild hyperbilirubinemia may reflect heart failure–related hepatic congestion in this patient with chronic heart failure; optimize diuretic therapy and assess volume status. 1

Optimize Heart Failure and Respiratory Management

• SGLT2 inhibitors reduce heart failure hospitalization independent of diabetes status and should be prioritized in this patient with chronic heart failure. 1

• Ensure guideline-directed medical therapy for heart failure (beta-blockers, ACE inhibitors/ARBs, mineralocorticoid receptor antagonists, diuretics) is optimized.

• Avoid volume overload, which worsens both heart and kidney function; adjust diuretic doses based on volume status and monitor for worsening kidney function.

• Withhold SGLT2i during prolonged fasting, surgery, or critical illness to reduce ketoacidosis risk. 1

Monitoring and Follow-Up

• Recheck eGFR, potassium, and bicarbonate 2–4 weeks after any medication change, then every 3–6 months in CKD stage 3a. 1, 5

• Monitor urine albumin-to-creatinine ratio annually to assess CKD progression and response to therapy. 1, 5

• Reassess platelet count and bilirubin in 4–6 weeks after initial workup; if stable or improving, continue current management.

• Refer to nephrology if eGFR declines by >5 mL/min/1.73 m² per year, albuminuria worsens despite therapy, or eGFR falls below 30 mL/min/1.73 m². 5

Common Pitfalls to Avoid

• Do not withhold SGLT2i or RAS inhibitors due to borderline laboratory abnormalities (platelets 140, bilirubin 1.6)—these medications reduce mortality and should be prioritized unless clear contraindications emerge. 1

• Do not stop RAS inhibitors for creatinine rises <30% within 4 weeks of initiation or dose increase. 1, 4

• Do not rely solely on A1C for glycemic assessment in advanced CKD (though eGFR 56 is not yet advanced); consider continuous glucose monitoring or frequent self-monitoring if A1C becomes unreliable. 2, 3

• Do not use dual RAS blockade (ACE inhibitor + ARB) as it increases acute kidney injury and hyperkalemia without benefit. 4

• Do not delay cardiovascular risk reduction while investigating mild laboratory abnormalities—this patient's mortality risk from cardiovascular disease and kidney failure far exceeds any risk from platelets of 140 or bilirubin of 1.6. 1