Addressing Pneumococcal Disease in CKD Patients: A Call for Preventive Action
In India, the prevalence of chronic kidney disease (CKD) has reached epidemic proportions, with population-based studies reporting a prevalence ranging from 4% to 20%.(1)
Chronic kidney disease (CKD) poses a significant burden on patients across all stages, with immune dysfunction contributing to a heightened vulnerability to infections. As CKD progresses, immune responses weaken, increasing susceptibility to infections such as pneumococcal disease. This burden intensifies in advanced CKD stages, including those on dialysis, where patients are up to ten times more likely to experience severe morbidity and mortality from pneumococcal disease compared to the general population. Despite advancements in healthcare, CKD patients remain highly vulnerable to infections and their clinical sequels, necessitating a proactive approach to preventive care, especially pneumococcal vaccination. (2)
Albuminuria, a key marker of kidney dysfunction, is observed in 7.1% of the population. Early stages of CKD dominate the spectrum, presenting a crucial opportunity for timely interventions to mitigate progression and infection-related risks. (3)
Pneumococcal Disease in CKD Populations- Intersection of Multiple Factors
Pneumococcal disease remains a leading cause of morbidity and mortality among patients with CKD. CKD patients, including those in earlier stages like stages 3 and 4, face an elevated risk of pneumococcal infections due to immune dysfunction and comorbidities such as COPD, diabetes, and cardiovascular disease. In end-stage renal disease (ESRD), CVD causes 50% of deaths, with a 10-20 times higher risk than the general population. (4) Hospitalization rates increase substantially with age, reaching 60-70% in older adults. Mortality from pneumococcal pneumonia ranges from 14% to 30% in general cases and escalates to 47% in severe community-acquired pneumonia (CAP). (5) CKD patients face rates of pneumococcal pneumonia ranging from 197 to 438 per 100,000, with risk ratios up to 13.9 times higher than healthy individuals. IPD rates in CKD patients are 26.8 to 57.9 per 100,000, with a risk ratio up to 14.6 times higher than in healthy populations. (6)
Pneumonia and CKD: Unique Risks and Management Challenges
Patients with CKD, especially those in advanced stages or on dialysis, have an increased risk of developing pneumonia due to a weakened immune system, the effects of uremia on immune cells such as neutrophils and lymphocytes, and common comorbidities such as diabetes, heart problems, and chronic lung diseases like COPD. (5,7) Management challenges include addressing the compounded risks from these comorbidities while ensuring timely interventions to prevent infection. COPD independently increases the risk of pneumonia in CKD patients with adjusted hazard ratios of 1.60 (95% CI, 1.54–1.67) for overall pneumonia, 1.89 (95% CI, 1.77–2.02) for outpatient pneumonia, and 1.41 (95% CI, 1.34–1.49) for inpatient pneumonia. (8)
A study from a tertiary care center reported that 19.1% of CKD patients developed pneumonia, with 61.5% in Stage 5 CKD. Among these, 60.3% required ICU care, 24.4% needed mechanical ventilation, and 28.2% succumbed to the infection. Hemodialysis patients face additional risks due to frequent vascular access and exposure to multidrug-resistant organisms, demonstrating the need for tailored infection management strategies. (6) Vaccination in the early stages of CKD has shown a better seroconversion rate compared to late vaccination, with patients vaccinated before the onset of dialysis demonstrating higher seroprotection rates and antibody titers. (9) Such evidence points towards the burning need for early intervention with vaccinations in CKD patients to optimize patient care outcomes.
CKD-induced immune dysfunction disrupts both innate and adaptive immunity and is characterized by hypercytokinemia, persistent inflammation, and impaired monocyte and neutrophil function. These changes result in diminished antigen presentation, weakened T-cell responses, and reduced immunological memory. Additionally, CKD patients often experience vaccine hyper-responsiveness, particularly in advanced stages, making early vaccination critical to optimize immune response. (10)
Recommended Vaccinations for Patients
For patients with CKD, vaccination is a cornerstone of preventive care. Several vaccinations are recommended for such patients, including the Hepatitis B vaccine, pneumococcal conjugate vaccine (PCV13), and pneumococcal polysaccharide vaccine (PPSV23). The PCV13 should be administered first, followed by the PPSV23 after eight weeks. Patients over the age of 60 should also receive herpes zoster and influenza vaccines to reduce infection risks further.(11) Booster doses of PPSV23 are recommended five years after the initial PPSV23 dose, particularly for patients aged 19-64 years, as per the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (12) and Association of Physicians of India guidelines on adult immunization. (13)
Early vaccination in CKD progression has demonstrated better seroconversion rates and stronger immune responses compared to vaccination at advanced stages. Patients in early-stage CKD can safely receive vaccines to prevent severe disease and improve long-term outcomes. (1)
Clinical and Hospitalization Outcomes Following Pneumococcal Vaccination
Pneumococcal vaccination significantly reduces hospitalization and mortality rates in CKD patients, who face a 14-16 times higher risk of death from pneumococcal infections. (6) Evidence suggests that immunization with PCV13 followed by PPSV23, or PCV13 alone, is associated with decreased one-year mortality in patients initiating dialysis. Vaccination also reduces pneumonia-related hospital admissions and cardiovascular complications associated with pneumococcal infections. (14) Moreover, PCV13 has shown a vaccine effectiveness of 61% (95% CI 24%–80%) in reducing pneumonia caused by Streptococcus pneumoniae in CKD patients with moderate kidney function (eGFR 30–59 mL/min/1.73 m²). (10)
Improving Vaccination Adherence- What can Doctors do?
To ensure adherence, CKD patients should be vaccinated promptly after diagnosis. For hospitalized patients, administering the initial dose during the first interaction with nephrologists can significantly improve compliance. Establishing patient education initiatives in clinics and providing follow-up reminders are essential strategies to enhance vaccine uptake. Vaccination programs integrated with insurance coverage can further encourage patients to complete their series. (2)
Normally, when you make a mistake, you get experience and learn. For CKD patients, it is imperative to prevent diseases like pneumonia rather than allowing them to experience suffering and learn the hard way. This is where vaccinations play a very important role. Vaccination is a key preventive measure for patients with CKD, with evidence indicating that adherence to immunization protocols significantly lowers infection rates, morbidity, and mortality in this immunocompromised population. In addition, adherence to recommended immunization schedules is essential to optimize patient outcomes.
Doctors have a crucial responsibility here, both in terms of patient education and consistent follow-up, to ensure that the patient’s health is safeguarded against preventable infections, fostering better long-term disease management and overall quality of life.
References:
1. Soni KK, Kalyanasundaram M, Singh S, Shubham S, Sabde YD, Prakash A, et al. Prevalence of chronic kidney disease among severely gas-exposed survivors in Bhopal, India. Natl Med J India 2023;36:5–10. DOI: 10.252549/NMJI_569_20
2. Stefaan J. Vandecasteele, Sara Ombelet, Sophie Blumental, Willy E. Peetermans, The ABC of pneumococcal infections and vaccination in patients with chronic kidney disease, Clinical Kidney Journal, Volume 8, Issue 3, June 2015, Pages 318–324, https://doi.org/10.1093/ckj/sfv030
3. Anand, Shuchi et al. “Prevalence of chronic kidney disease in two major Indian cities and projections for associated cardiovascular disease.” Kidney international vol. 88,1 (2015): 178-85. doi:10.1038/ki.2015.58
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7. Pant, Abhishek et al. “Pneumonia in Patients with Chronic Kidney Disease Admitted to Nephrology Department of a Tertiary Care Center: A Descriptive Cross-sectional Study.” JNMA; journal of the Nepal Medical Association vol. 59,242 1000-1003. 15 Oct. 2021, doi:10.31729/jnma.7074
8. Chou CY, Wang SM, Liang CC, Chang CT, Liu JH, Wang IK, Hsiao LC, Muo CH, Huang CC, Wang RY. Risk of pneumonia among patients with chronic kidney disease in outpatient and inpatient settings: a nationwide population-based study. Medicine (Baltimore). 2014 Dec;93(27):e174. doi: 10.1097/MD.0000000000000174.
9. Guidelines for vaccination in patients with chronic kidney disease. Indian J Nephrol. 2016 Apr;26(Suppl 1):S15–8. PMCID: PMC4928524.
10. Haddiya, Intissar. “Current Knowledge of Vaccinations in Chronic Kidney Disease Patients.” International journal of nephrology and renovascular disease vol. 13 179-185. 27 Jul. 2020, doi:10.2147/IJNRD.S231142
11. Guidelines for vaccination in patients with chronic kidney disease.Indian Journal of Nephrology vol. 26,Suppl 1 (2016): S15–S18.
12. Le, Dustin et al. “Pneumococcal vaccination effectiveness (PCV13 and PPSV23) in individuals with and without reduced kidney function: a test-negative design study.” Clinical kidney journal vol. 17,6 sfae145. 8 May. 2024, doi:10.1093/ckj/sfae145
13. Indian Consensus Guideline on Adult Immunization. Association of Physician of India 2024. Retrieved on 11 December 2024 from https://www.emvac.in/wp-content/uploads/2024/06/Adult-Vaccination-Booklet.pdf
14. Pierre, Élodie et al. “Pneumococcal vaccination coverage at the initiation of chronic dialysis, and its association with mortality during the first year.” Vaccine vol. 41,24 (2023): 3655-3662. doi:10.1016/j.vaccine.2023.05.003
