What is the diagnosis and treatment for a patient with hyperglycemia, hypercalcemia, and impaired renal function?

Diagnosis and Treatment

Primary Diagnosis

This patient most likely has multiple myeloma with cast nephropathy causing acute kidney injury, hyperglycemia (diabetes), and hypercalcemia. The constellation of impaired renal function (GFR 56, creatinine 1.37), hypercalcemia (calcium 10.3), and hyperglycemia (glucose 184, A1c 7.9) in a male patient strongly suggests multiple myeloma until proven otherwise 1.

Immediate Diagnostic Workup

• Obtain serum free light chains (FLC) immediately - FLC concentrations >50 mg/dL significantly increase the risk of acute kidney injury in multiple myeloma, and levels >80-200 mg/dL dramatically increase this risk 1
• Order serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), and immunofixation to identify monoclonal proteins 1
• Check complete blood count for anemia and thrombocytopenia
• Obtain skeletal survey or whole-body low-dose CT to assess for lytic bone lesions
• Measure intact parathyroid hormone (PTH) to differentiate PTH-dependent from PTH-independent hypercalcemia 2

Urgent Treatment Protocol

For Suspected Multiple Myeloma with Renal Impairment

This is a medical emergency requiring immediate intervention 1. The treatment priorities are:

1. Aggressive hydration with intravenous normal saline - Target urine output of 100-150 mL/hour to decrease renal tubular light chain concentration 3, 1

2. Treat hypercalcemia immediately with:

   • Continue IV saline hydration 3, 2
   • Administer bisphosphonates (pamidronate with dose adjustment for renal function or zoledronic acid) 3
   • Consider calcitonin for rapid effect if symptomatic 3, 2
   • Avoid denosumab initially due to risk of severe hypocalcemia with rapid tumor lysis 3

3. Discontinue all nephrotoxic medications including NSAIDs 3, 1

4. Initiate bortezomib-based chemotherapy urgently if multiple myeloma is confirmed - Bortezomib does not require dose adjustment in renal failure and rapidly reduces FLC levels 1

   • Target: >50-60% reduction in serum FLC for renal recovery 1
   • Goal: Achieve FLC <50 mg/dL by end of cycle 1 1

For Diabetes Management with Stage 3a CKD

Start metformin immediately since the eGFR of 56 mL/min/1.73 m² is well above the 30 mL/min/1.73 m² safety threshold 3, 4, 5, 6. The FDA label confirms metformin is contraindicated only when eGFR <30 mL/min/1.73 m² 6.

Add an SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin) immediately for substantial cardiorenal protection, as the eGFR ≥30 mL/min/1.73 m² meets the threshold for use 3, 4, 5.

Important caveat: If hypercalcemia is confirmed and SGLT2 inhibitor is started, monitor calcium levels closely as SGLT2 inhibitors may predispose to hypercalcemia through dehydration from osmotic diuresis and reduced calcium excretion 7. Given the existing hypercalcemia, delay SGLT2 inhibitor initiation until calcium normalizes to avoid exacerbating hypercalcemia.

Target HbA1c of 7-8% for this patient with moderate CKD, as more intensive targets increase hypoglycemia risk without clear mortality benefit 4, 5.

If glycemic targets are not met with metformin alone, add a GLP-1 receptor agonist (liraglutide, semaglutide, or dulaglutide) for cardiovascular benefits and potential to prevent eGFR decline 3, 4, 5.

Monitoring Protocol

• Recheck serum calcium, creatinine, and electrolytes within 24-48 hours after initiating treatment 3, 2
• Monitor FLC levels at day 12 and day 21 if multiple myeloma confirmed - Earlier FLC reduction correlates with better kidney recovery 1
• Recheck blood chemistry 1-2 weeks after metformin initiation and 1-2 weeks after final dose titration 3
• Monitor HbA1c every 3 months until stable, then every 6 months 4
• Assess eGFR at least annually, more frequently given age and renal impairment 3, 6

Critical Pitfalls to Avoid

• Do not dismiss mild hypercalcemia (10.3 mg/dL) - Even modest elevations can cause acute renal failure, especially when combined with other nephrotoxic factors 2
• Do not delay treatment waiting for definitive multiple myeloma diagnosis - Prompt FLC reduction is critical for renal recovery 1
• Do not use long-acting sulfonylureas (glyburide) at any level of renal function due to hypoglycemia risk 5
• Do not start SGLT2 inhibitor until hypercalcemia is corrected to avoid worsening calcium levels 7
• Do not withhold metformin unnecessarily - It is safe and recommended at this eGFR level 3, 4, 6
• Monitor for lactic acidosis symptoms (malaise, myalgias, abdominal pain, respiratory distress) when using metformin, especially if renal function declines 6

Lifestyle Modifications

• Moderate-intensity physical activity for at least 150 minutes per week 3, 4, 5
• Maintain protein intake at approximately 0.8 g/kg/day 3, 4
• Limit sodium intake to <2 g/day (<5 g sodium chloride) 3, 4
• Avoid excessive alcohol intake due to increased risk of lactic acidosis with metformin 4, 6