What are the general principles and treatment approaches in internal medicine for managing common adult diseases, such as hypertension, diabetes, and heart disease, in a patient with potential comorbid conditions and impaired renal function?

Managing Common Adult Diseases in Internal Medicine: Hypertension, Diabetes, and Heart Disease with Comorbid Renal Impairment

For adults with hypertension, diabetes, and heart disease complicated by impaired renal function, initiate ACE inhibitors or ARBs as first-line therapy when albuminuria ≥30 mg/g is present, add SGLT2 inhibitors immediately when eGFR ≥20 mL/min/1.73 m², and target blood pressure <130/80 mmHg while monitoring renal function closely. 1, 2

Blood Pressure Management in Renal Impairment

Target Blood Pressure Goals

• Target systolic BP <130 mmHg in all patients with CKD and albuminuria ≥30 mg/g; target <140/90 mmHg if albuminuria <30 mg/g. 1, 2
• For patients with diabetes and CKD, the stricter target of <130/80 mmHg applies regardless of albuminuria level. 1
• Patients with renal insufficiency or heart failure require drug therapy initiation when BP ≥130/85 mmHg (≥130/80 mmHg for diabetics). 1

First-Line Antihypertensive Selection

• Initiate ACE inhibitor or ARB as first-line therapy for all patients with albuminuria ≥30 mg/g, titrating to maximum tolerated doses. 1, 2
• For albuminuria ≥300 mg/g, ACE inhibitor or ARB use is a strong recommendation based on reduction in cardiovascular events and renal protection. 1, 2
• Monitor serum creatinine and potassium within 2-4 weeks after starting or dose escalation. 2
• Continue therapy unless creatinine rises >30% within 4 weeks of initiation. 2
• Never combine ACE inhibitors with ARBs—this increases adverse events without additional benefit. 2

Additional Antihypertensive Agents

• Add a long-acting dihydropyridine calcium channel blocker as second-line agent if BP remains uncontrolled on ACE inhibitor/ARB. 2
• Thiazide diuretics should be used for most patients, either alone or combined with other classes, but switch to loop diuretics when eGFR <30 mL/min/1.73 m². 1
• For BP >20 mmHg above systolic goal or >10 mmHg above diastolic goal, consider initiating two agents simultaneously, one typically being a thiazide diuretic. 1
• Restrict sodium intake to <2 g/day to optimize antihypertensive effectiveness and reduce volume overload. 1, 2

Diabetes Management with Renal Impairment

SGLT2 Inhibitors: First-Line Kidney Protection

• Initiate SGLT2 inhibitor immediately when eGFR ≥20 mL/min/1.73 m², regardless of glycemic control, as this provides kidney protection and cardiovascular benefits independent of glucose lowering. 1, 2
• Continue SGLT2 inhibitors until dialysis or transplantation, even as eGFR declines below 20 mL/min/1.73 m². 1, 2
• This represents the most important recent advance in diabetic kidney disease management, with benefits extending beyond glucose control to include heart failure prevention and slowing CKD progression. 1

Metformin Dosing by Renal Function

• Metformin can be added when eGFR ≥30 mL/min/1.73 m² for additional glycemic control. 2, 3
• Reduce metformin to maximum 1000 mg daily when eGFR 30-44 mL/min/1.73 m². 2, 3
• Discontinue metformin when eGFR <30 mL/min/1.73 m² due to lactic acidosis risk. 2, 3
• Initiation of metformin is not recommended in patients with eGFR between 30-45 mL/min/1.73 m². 3
• Assess eGFR before initiating metformin and periodically thereafter; in elderly patients or those at risk for renal impairment, assess more frequently. 3

Additional Glucose-Lowering Agents

• Add GLP-1 receptor agonist if glycemic targets are unmet or if SGLT2 inhibitors/metformin cannot be used. 1, 2
• Consider finerenone (nonsteroidal mineralocorticoid receptor antagonist) for persistent albuminuria ≥30 mg/g despite first-line therapy when potassium is normal. 1, 2

Glycemic Targets

• Target HbA1c between 6.5-8.0%, individualized based on hypoglycemia risk, life expectancy, and comorbidities. 1, 2
• For healthy older adults with few coexisting illnesses, target HbA1c <7.5%. 1
• For complex/intermediate health status (multiple chronic illnesses or mild-to-moderate cognitive impairment), target HbA1c <8.0%. 1
• For very complex/poor health (end-stage chronic illnesses or moderate-to-severe cognitive impairment), target HbA1c <8.5%. 1
• Check HbA1c every 3 months when adjusting therapy, at least twice yearly when stable. 2

Dietary Protein Restriction

• Limit dietary protein to 0.8 g/kg/day for non-dialysis CKD patients to slow progression of kidney disease. 1, 2

Heart Disease Management

ACE Inhibitors/ARBs for Cardiovascular Protection

• ACE inhibitors reduce onset of heart failure and new-onset diabetes in patients with diabetes or other cardiovascular complications. 1
• ARBs (losartan, irbesartan) significantly reduce heart failure incidence in patients with type 2 diabetes and nephropathy. 1
• For patients with established atherosclerotic disease, long-term ACE inhibitor treatment decreases cardiovascular death, MI, and stroke risk. 1
• In heart failure patients or those with left ventricular dysfunction, ACE inhibitors reduce death, recurrent MI, and progression to persistent heart failure. 1

Beta-Blockers

• Beta-blockers reduce all-cause mortality, reinfarction, and CHD death in post-MI patients. 1
• In heart failure patients, beta-blocker therapy reduces all-cause mortality. 1

Cardiovascular Risk Reduction

• Initiate statin therapy in all CKD patients with diabetes, targeting LDL-C <100 mg/dL (consider <70 mg/dL for very high risk). 1, 2
• Statins should treat all diabetic CKD patients stages 1-4 with LDL-C >100 mg/dL. 2
• Do not initiate statins in type 2 diabetics on maintenance hemodialysis without specific cardiovascular indication. 2
• Obtain 12-lead ECG to assess for left ventricular hypertrophy and arrhythmias. 2
• Consider echocardiography if ECG abnormal or cardiac symptoms present. 2

Lifestyle Modifications

• Recommend tobacco cessation for all tobacco users. 1, 2
• Advise moderate-intensity physical activity ≥150 minutes weekly, compatible with cardiovascular tolerance. 1, 2
• Emphasize consumption of fruits, vegetables, whole grains, lean poultry, fish, and legumes while discouraging processed foods with excess saturated fat, salt, and sugar. 1

Monitoring for CKD Complications

Frequency of Monitoring

• Begin monitoring for anemia, bone disease, metabolic acidosis, and hyperkalemia when eGFR <60 mL/min/1.73 m² (Stage 3). 2
• Check serum creatinine, eGFR, and urine albumin-to-creatinine ratio at least annually for moderate-to-severe CKD. 2
• For eGFR <60 mL/min/1.73 m² or GFR decline ≥4 mL/min/1.73 m²/year, monitor every 1-6 months. 2
• Monitor hyperkalemia particularly in patients on ACE inhibitors/ARBs—attempt dietary modification, diuretics, sodium bicarbonate, or GI cation exchangers before discontinuing RAAS blockade. 2

Acute Kidney Injury Prevention

• All CKD patients are at increased risk for acute kidney injury—avoid nephrotoxins and monitor during volume depletion. 2
• Discontinue metformin at the time of, or prior to, iodinated contrast imaging procedures in patients with eGFR 30-60 mL/min/1.73 m²; in patients with liver disease, alcoholism, or heart failure; or when intra-arterial contrast will be administered. 3
• Re-evaluate eGFR 48 hours after imaging; restart metformin if renal function is stable. 3

Nephrology Referral Criteria

• Refer to nephrologist when eGFR <30 mL/min/1.73 m² (Stage 4), or earlier if uncertainty about etiology, difficult management issues, or rapid progression. 1, 2
• Specific indications include: eGFR <30 mL/min/1.73 m², albuminuria ≥300 mg/g despite treatment, rapidly declining kidney function, resistant hypertension, or electrolyte disturbances. 2
• Early referral (Stage 4) reduces cost, improves quality of care, and delays dialysis. 2
• Preparation for kidney replacement therapy should begin during Stage 4, well before uremic symptoms develop. 2

Critical Pitfalls to Avoid

• Never restrict protein intake excessively during acute illness, as this worsens catabolism and outcomes. 4
• Avoid NSAIDs, which worsen renal function, reduce diuretic effectiveness, and increase hyperkalemia risk. 1, 2, 5
• Do not delay nephrology referral if creatinine continues rising despite appropriate interventions. 4
• Excessive diuresis can precipitate acute kidney injury in CKD patients with reduced renal reserve. 5
• Monitor for hypokalemia with higher diuretic doses; potassium supplementation may be necessary. 5
• Assess for volume depletion from diarrhea or other causes, which can precipitate prerenal azotemia requiring immediate volume repletion with isotonic saline. 4