Early Intervention and Treatment of Chronic Kidney Disease

Chronic kidney disease (CKD) affects more than 1 in 7 US adults—an estimated 35.5 million Americans.¹ For patients with high blood pressure and diabetes, the 2 most common causes of CKD, the risk of CKD is even higher.¹ Patients with CKD are often asymptomatic in the primary stages and may go undetected, raising concerns about delayed diagnosis and the risk for increased morbidity.²  Research by Levey et al indicates that CKD prevalence is affected by ethnicity, geographic region, and ancestry.² Ethnicity and region can also be associated with variation in access to quality healthcare.² Educating our patients and health care providers in primary care and specialty care settings is vital to improve the detection and treatment of patients with CKD.

Overview of CKD

CKD is defined as an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73 m² or an eGFR greater than 60 mL/min/1.73 m² with concomitant injury of the renal structure for at least 3 months.³ Factors used to gauge renal injury include albuminuria, hematuria, leukocyturia, persistent electrolyte imbalances, renal imaging abnormalities, histologic biopsy changes in the kidney, and previous kidney transplant.³

Calculation of eGFR allows for the underlying cause of kidney damage to be more thoroughly assessed using factors such as filtration markers and albuminuria.³ Creatinine is the filtration marker most often used in calculations, but in some patients whose creatinine levels may be altered, cystatin C is preferred.³ The eGFR, which commonly is used to stage CKD, breaks the disease into 5 stages: stage 1 (GFR ≥90 mL/min/1.73 m²), stage 2 (GFR 60-89 mL/min /1.73m²), stage 3a (GFR 45-59 mL/min/1.73 m²), stage 3b (GRF 30-44 mL/min/1.73 m²), stage 4 (GRF 15-29 mL/min/1.73 m²), stage 5 (GFR <15 mL/min per 1.73 m²) (Table 1).³

Another common method used to assess kidney function is the urine to albumin creatinine ratio (ACR), which is preferred over the urine protein to creatinine ratio due to standardization of scale and accuracy markers.³ When using urine as an estimator, it is more accurate to use a first morning or 24-hour urine collection.³ The 3 stages of CKD in relation to albuminuria are as follows: stage 1 (urine ACR <30 mg/g), stage 2 (30-300 mg/g), and stage 3 (>300 mg/g) (Table 2).³ 

Table 1. 5 Stages of CKD using eGFR

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate

Table 2. Stages of CKD using Urine ACR

ACR, albumin creatinine ratio; CKD, chronic kidney disease

CKD is an irreversible disease process; thus, the main goal in management is to slow the progression of the disease, manage comorbid conditions, improve quality of life, and prevent end-stage renal disease (ESRD) and transplantation.⁴ CKD management is multifactorial and requires careful monitoring to provide patients with the best prognosis. The most widely used guideline for the management of CKD comes from Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.⁴ The KDIGO panel suggests that one of the most important ways to manage CKD is by reducing the risk for cardiovascular disease.⁴

When managing blood pressure and cardiac disease in patients with CKD, clinicians commonly refer to KDIGO guidelines and the Eighth Joint National Committee (JNC8).^4,5 The goal of blood pressure management is to maintain a pressure no higher than 140/90 mmHg, but if a patient’s ACR places them in stage 1 or higher, further modifications may be necessary.³ Current treatment guidelines for hypertension (HTN) management include the use of either angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers; it should be noted that because these medications have similar side effect profiles, they are not recommended for joint use.

Along with control of blood pressure, proper glycemic control in patients with diabetes mellitus (DM) has been shown to improve patient outcomes.³ DM management recommendations include maintaining a hemoglobin A1c of 7.0% and adjusting dosages for medications cleared through the kidneys.³ Studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) provide benefit in diabetic patients and additionally have benefit in reducing cardiovascular disease in patients with DM.^6-8 

Patients with CKD should be advised to avoid nephrotoxins such as nonsteroidal anti-inflammatory drugs. Dosage adjustments of other medications may need to be made because people with CKD are at a higher risk of having adverse drug effects. Care should be personalized to each individual’s case of CKD, and related complications, such as anemia, electrolyte and mineral abnormalities, bone disorders, and dietary issues, need to be evaluated in the management plan. Patients should be educated about lifestyle modifications and how to properly take any medications and encouraged to adhere to the plan of care. Finally, as the disease progresses and eGFR falls below stage 4 or ACR falls below stage 3, patients should be referred to a nephrologist.³

Comorbidities in CKD

HTN and DM are the most common risk factors contributing to CKD, along with non-risk factors/comorbidities such as inflammation, gut dysbiosis, uremic retention solutes, fibrosis, and bone disease.^9,10 Renal dysfunction and related comorbidities cause intestinal inflammation, which leads to bacterial growth dysfunction.⁹  In addition, when the gut is not functioning properly, it causes an increase in uremic toxins and proteolytic metabolism, which activates a chronic immune response, which, in turn, increases the risk for infection, malignancy, hospitalization, and death.⁹

There is an increase in the number of metabolites filtering through the kidneys, specifically, trimethylamine, which is used as an indicator to measure the severity of renal function in patients.⁹

Recognizing that improved management of comorbid diseases in patients with CKD can have positive outcomes, Li et al performed a retrospective cohort study to evaluate how the management of CKD and comorbid disease can concomitantly reduce healthcare resource utilization costs and disease burden on a patient.¹¹ With the help of funding from Humana Healthcare Research, the researcher evaluated patients enrolled in a Medicare Advantage Prescription Drug plan who had concomitant stage 3a or greater CKD in 2017.¹¹ Participants were required to maintain regular scheduled office visits to properly manage their CKD and other comorbid conditions. The researchers found that optimized disease management, especially when focusing on comorbid conditions such as HTN and DM, resulted in a reduction in healthcare resource utilization and medical costs at 1 year. This information is helpful for primary care provider settings because it shows how to reduce costs associated with HTN and DM and shift resources to be allocated toward nephrology management.

Importance of Early Recognition and Treatment of CKD

In its 2023 report on CKD in the United States, the Centers for Disease Control and Prevention (CDC) estimated that approximately 35 million adults have CKD.¹ Recent data shows that 9 in 10 adults do not know they have CKD, and of those, 1 in 3 have severe CKD.¹  Organizations such as the Kidney Early Evaluation Program, National Institutes of Health, and Kidney Disease Education Program are spearheading initiatives focused on promoting early screening and detection in an effort to curb disease progression.¹²

At a minimum, higher-risk individuals should be screened with evaluations for blood pressure, eGFR, urine ACR, and urine screen; in addition, diagnostic imaging using computed tomography or ultrasound should be obtained.¹² Evidence supports providers exploring any associated symptoms (ie, neuropathy, urinary hesitancy, rash) in individuals with suspicion of disease.³

Point-of-care ultrasound is a diagnostic tool used to diagnose and assess for heart failure, ascites, blood clots, and many other medical conditions. It has become a useful tool for assessing kidney structure and function; however, there is insufficient evidence about whether ultrasound should be used as an independent factor alone without follow up and lab analysis.¹³ Although more research needs to be conducted to establish efficient ways to use ultrasound for early detection, it can provide additional information when creating a holistic plan of care for a patient.

Primary Care Role in CKD

CKD requires providers to ensure adequate time management due to the complexity of the disease, but with a limited timeframe during patient visits, they must prioritize immediate patient needs while evaluating and interpreting labs that may not correlate with symptoms. In early stages of the disease, patients rarely have signs of CKD when presenting to their primary care office; thus, risk factor assessment should never be overlooked. Vital signs and lab checks, including blood pressure, blood sugar, and urine collection, should be routine.¹⁴ The Kidney Disease Outcomes Quality Initiative guide recommends regular screening of patients who present with comorbid conditions such as HTN and DM, but does not recommend this screening for patients without such comorbidities.¹⁵

Quick response to primary and secondary CKD care can facilitate a more favorable disease progression for the patient.¹⁶ Nagib et al showed that recognition of stage 1-3 CKD in the primary care setting results in fewer complications and increases the chance that patients can receive renal replacement therapy through dialysis or renal transplant.¹⁶ The research proves the relevance of working with primary care providers to formulate a health care plan that meets the needs of patients but does not disrupt the needs of the primary care workplace.

Burden of CKD on Patients

Managing CKD and its comorbid conditions properly can help reduce the financial burden on a patient, but finances are not the only burden CKD places on patients.¹³ CKD patients experience a great deal of mental distress, have difficulty maintaining employment, and have reduced quality of life.¹⁷ As rates of mental illness rise, it is important to address the correlation between mental illness and CKD. As CKD progresses, patients experience symptoms including appetite loss, nausea, vomiting, and, ultimately, having to undergo tri-weekly dialysis sessions that leave them weak and unable to perform activities of daily living. Patients with these symptoms, as well as those with functional gastrointestinal disorders, have been shown to have increased rates of anxiety and depression.¹⁸ There are initiatives in place to conduct further research on how to reduce these negative side effects with routine patient-reported outcomes assessments and collaborative behavioral health interventions.¹⁷

Education

As CKD research continues to grow, it is important that health care providers use continuing education and learning resources in their spare time so they, in turn, can provide appropriate education to patients.  The best learning happens in small increments over a period, with knowledge checkpoints to aid in long-term memory retention.¹⁹ As providers get to know their patients, they learn how to best cater to their needs and empower them to take action to support their health. Naber and Purohit evaluated a kidney-friendly diet to reduce the severity of CKD, noting that careful regulation of protein, phosphorus, sodium, potassium, and calcium intake has shown positive results in alleviating symptoms of CKD.²⁰ Taking the time to educate patients on their diet is an easy and efficient way providers can address attainable measures a patient can implement to be a part of their life for a better diagnostic outcome.

Conclusion

Patients with CKD face many barriers, including a high screening burden and increased risks for mortality and morbidity. CKD diagnoses continue to rise each year, and the healthcare field needs to work together to minimize the number of patients who go undetected until later stages of the disease, when damage is irreversible. Thus, screening and treating patients early for kidney disease is so important to allow them to have the best possible quality of life. Literature continues to encourage time-efficient care and communication between healthcare teams, especially among primary care providers and specialists. Working together, multidisciplinary providers can help streamline patient care and increase patient trust in providers.