What is the next step in managing an elderly female patient with pulmonary hypertension, Heart Failure with preserved Ejection Fraction (HFpEF), severe Chronic Obstructive Pulmonary Disease (COPD), and stage 4 Chronic Kidney Disease (CKD) who has shown improvement in symptoms with diuresis, Guideline-Directed Medical Therapy (GDMT), and sildenafil, but has developed worsening renal function from impaired to severely impaired?

From the Guidelines

The patient's declining renal function requires immediate attention, and I recommend temporarily holding sildenafil and reassessing the diuretic regimen, as both may be contributing to the worsening kidney function. Consider reducing the diuretic dose by 50% while closely monitoring volume status, as high doses of diuretics can lead to volume contraction, increasing the risk of hypotension and renal insufficiency 1. Nephrology consultation is essential at this stage of CKD progression (GFR now approximately 13 ml/min). Laboratory monitoring should include electrolytes, BUN, creatinine, and BNP twice weekly initially.

Regarding GDMT (guideline-directed medical therapy), continue ACE inhibitors or ARBs at the lowest effective dose with close monitoring, as they provide cardioprotective benefits despite potentially affecting GFR 1. Beta-blockers should be maintained if hemodynamically tolerated. For volume management, consider transitioning to a loop diuretic with better bioavailability in advanced CKD, such as torsemide 10-20mg daily or bumetanide 0.5-1mg daily, as these have been shown to improve symptoms and exercise tolerance in patients with HF 1.

Some key considerations for managing this patient include:

• Dietary sodium restriction to <2g/day and fluid restriction to 1.5L/day are crucial to reduce fluid overload and alleviate symptoms.
• The patient should be evaluated for renal replacement therapy options given the GFR <15, which defines end-stage renal disease.
• Regular reassessment of the balance between heart failure management and renal protection is necessary to optimize outcomes in this complex patient.
• The worsening renal function likely results from a combination of cardiorenal syndrome, medication effects, and progression of underlying CKD, highlighting the need for careful management and monitoring.

From the FDA Drug Label

In volunteers with severe (CLcr less than 30 mL/min) renal impairment, sildenafil clearance was reduced, resulting in approximately doubling of AUC and Cmax compared to age-matched volunteers with no renal impairment In addition, N-desmethyl metabolite AUC and Cmax values were significantly increased 200 % and 79 %, respectively, in subjects with severe renal impairment compared to subjects with normal renal function

• The patient's renal function has dropped from 30 to 13, indicating severe renal impairment.
• Sildenafil clearance is reduced in severe renal impairment, which may lead to increased plasma concentrations of sildenafil and its active metabolite.
• Considering the patient's severe renal impairment and the potential for increased sildenafil concentrations, caution is advised.
• The FDA drug label suggests that sildenafil exposure may be increased in patients with severe renal impairment, which may increase the risk of adverse effects.
• Dose adjustment or close monitoring of the patient's condition may be necessary to minimize potential risks 2.

From the Research

Patient's Condition

The patient is an elderly female with breathlessness, pulmonary hypertension, HFpEF, severe COPD, and CKD4. Her BNP was high, and she was clinically overloaded. She was treated with diuresis and started on GDMT, as well as sildenafil. Over time, her symptoms improved, but her renal function dropped from 30 to 13.

Renal Function Decline

• The decline in renal function could be due to various factors, including the progression of underlying kidney disease 3.
• However, it is essential to note that the patient's renal function decline may not be solely due to the progression of kidney disease, as some studies suggest that compromised renal function does not necessarily result in further decline 3.
• The use of sildenafil in patients with pulmonary arterial hypertension has been shown to improve renal function in some studies 4.

Sildenafil Treatment

• Sildenafil has been shown to improve exercise capacity, WHO functional class, and hemodynamics in patients with symptomatic pulmonary arterial hypertension 5.
• In patients with HFpEF and combined pre- and postcapillary pulmonary hypertension, sildenafil has been associated with improved exercise capacity, pulmonary hemodynamic parameters, and right ventricular function 6.
• However, the effect of sildenafil on renal function in patients with CKD4 and pulmonary hypertension is not well established.

Potential Next Steps

• Close monitoring of the patient's renal function and adjustment of medications as needed.
• Consideration of alternative treatments or dose adjustments to minimize the decline in renal function.
• Further evaluation of the patient's underlying kidney disease and its progression to determine the best course of treatment.