Stage 3 chronic kidney disease (CKD) is estimated to affect over 30 million adults in the United States. Patients with advanced CKD, defined for our purposes as stage 4 and 5, will often have ongoing follow ups with a nephrologist. However, in CKD stage 3 (defined as eGFR 30-59mL/min), the primary-care physician will often be at the helm of treatment. Managing CKD stage 3 can be complex; having a clinical pharmacist meet with your CKD patients prior to their office visit helps to prepare both the patient and you to have the most comprehensive and efficient visit possible.
MM is a 63-year-old white male patient to be seen by his PCP for an annual wellness visit (AWV) and referred to meet with an RxLive clinical pharmacist for hypertension medication management prior to that AWV.
Vitals: BP 151/95, BMI: 38
Medications: HCTZ 25mg QAM, Ibuprofen 600mg TID PRN pain
Labs: eGFR: 51mL/min, Urine albumin: 68mg/dL
The RxLive clinical pharmacist meets with MM and notes that he has stage 3 CKD with moderately increased proteinuria. In collaboration with the patient, the clinical pharmacist establishes the following plan:
- Reduce BP to goal range <130/80mmHg to protect renal function and reduce proteinuria
– The patient agrees to start lisinopril 10mg daily with a 1-month follow up to check SCr, K+ and home BP readings
- Reduce exposure to nephrotoxic drugs by providing patient education and stopping ibuprofen and starting Acetaminophen 650mg Q6H PRN pain
First, the markers of severity of CKD need to be discussed. We all use some measure of renal function on a daily basis, but there is some nuance in understanding which measure is most appropriate.
eGFR vs CrCl
Both of these calculations can be extremely useful for measuring the degree of renal impairment, but because they’re calculated slightly differently, there can be significant discordance between them. Some online calculators can help providers determine which calculation method is likely to be most accurate for their individual patients. The National Kidney Foundation also publishes a more in-depth explanation of the nuances of each method for estimating renal function. Regardless of the preferred calculation, it’s important to remember that trends over time are usually much more important than any single value.
When looking at drug dosing in renal impairment, most drugs which require dose adjustments will have recommendations based on CrCl. However, there are some notable exceptions like metformin.
Once current renal function is assessed, proteinuria is an important prognostication factor. The degree of proteinuria has a strong association with progression of renal disease, so reducing proteinuria seems to be an important surrogate treatment goal. Thus, medications which reduce proteinuria can be important for slowing the progression of kidney disease. Additionally, non-drug treatments of albuminuria include recommendations for weight loss, sodium restriction and tobacco cessation.
CKD as a risk for CVD
Although CKD stage 3 is obviously an important risk factor for more advanced kidney disease, many PCPs are unaware that stage 3 CKD patients are at up to 20-fold higher risk of death from a cardiovascular event than they are from kidney disease. Cardiovascular risk reduction is an extremely important consideration when managing CKD patients. Let’s dive into the finer points of managing CVD disk in patients with CKD.
Lipid management: SHARP showed us that treating hyperlipidemia in CKD patients reduces major vascular events. The likely mechanism of benefit is the same as in patients with normal renal function; statins reduce the deposition of atherosclerotic plaques and stabilize existing plaques. Most statins don’t require renal dose reductions. Rosuvastatin is a notable exception here, requiring dose adjustments in more advanced CKD.
Hypertension management: A large meta-analysis determined we need to be aggressive with treating hypertension in CKD to slow progression of the disease. This review suggested systolic BP goals of 110-129 mm/Hg as the optimal range for slowing progression. This is in line with guideline recommendations as well.
Angiotensin converting enzyme inhibitors (ACEi) and Angiotensin II receptor blockers (ARB) are the drugs of choice here and can reduce proteinuria by about 30%. They work by changing the hemodynamics within the kidney and essentially reducing blood pressure within the nephron. These agents essentially help the kidney by slowing down its workflow, and as such, an increase in SCr and corresponding reduction in calculated is to be expected within the first couple of weeks. As long as this increase doesn’t exceed about 35% and it stabilizes within a couple of months, this doesn’t represent a reason to stop or change ACEi/ARB therapy.
Thiazide diuretics like chlorthalidone are the next line agents for BP reduction, although they can lose their clinical effects in creatinine clearance < 20-30mL/min. Note that chlorthalidone is generally the agent of choice in this class for all hypertensive patients due to its long half-life, resulting in more consistent BP control. Interestingly, non-dihydropyridine calcium channel blockers (diltiazem and verapamil) also can reduce proteinuria but aren’t often thought of in this context and tend to have more drug interactions than other antihypertensive agents. Loop diuretics such as furosemide can be extremely useful for patients with fluid retention issues. Unlike the thiazides, the loops can be useful down to very low levels of renal function.
Diabetes is one of the most common causes of CKD in the U.S. Tightening glycemic control has long been known to reduce the risk of progression of CKD. Some treatments, such as sodium glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to significantly reduce progression of CKD, and should be considered as early add-on therapy in suboptimally controlled type-2 diabetes.
Protecting residual renal function
It’s particularly important in CKD3 to limit exposure to nephrotoxic drugs such as NSAIDs, aminoglycosides and contrast media whenever possible.
Chronic kidney disease is an extremely common condition among patients seen in primary care clinics. Fortunately, many of the things we’re already doing to protect the cardiovascular system are also helpful in slowing the progression of CKD.