Reducing Inflammatory Markers in Chronic Kidney Disease (CKD) - Role of Probiotics

Need for delaying the disease progression-Progression of CKD is a significant concern while managing patients in stages G1-4. The progression of CKD to life-threatening end-stage renal disease (ESRD) remains a severe socio-economic burden despite advancements in managing the disease. (1)

• Hypertension remains one of the most damaging complications of CKD and contributes to the progressive decline in kidney function, cardiovascular diseases (CVD), and related mortality. (3)
• The risk of mortality from CVD is 8.1-fold greater in a patient with CKD stage G5 A3 (eGFR < 15 ml/min per 1.73 m2 and urinary albumin-creatinine ratio > 300 mg/g) than in a reference population without kidney disease. (3)
• Chronic kidney disease (CKD) is linked to several adverse clinical outcomes, including cardiovascular events, kidney failure requiring renal replacement treatment, cardiovascular disease, anaemia, mineral bone disorder, volume overload, electrolytes, and acid-base abnormalities and death, deteriorating overall poor quality of life for patients. (3)
• CKD exacerbates the significant burden and public health consequences of both communicable and non-communicable diseases. (3)

Due to the direct link of such life-threatening consequences to CKD progression, there remains an urgent need to control the disease in its initial stages.

Role of Inflammatory Markers in CKD-According to studies, inflammatory indicators indicate renal function deterioration. (4)

• Previous studies have found a correlation between CKD and elevated C-Reactive proteins (CRP) levels and a link between CRP and cardiovascular risk in ESRD patients.
• Research along these lines have found that inflammation, as measured by CRP levels, correlated with endothelial dysfunction and atherosclerotic alterations in CKD patients.
• The advancement of kidney disease (CKD stages 1-4) is associated with a rise in inflammatory and procoagulant indicators such as CRP, fibrinogen, and coagulation factor VIII, as well as an increase in leukocyte average values.
• Another study in a larger cohort of CKD patients, which looked at the relationship between albuminuria, renal function, and inflammatory biomarkers, discovered that individuals with decreased eGFR had higher levels of IL-1, IL-1RA, IL-6, TNF-, TGF-, CRP, and fibrinogen.

The link between CKD and inflammation, as well as the demonstrated link between inflammation and CV risk, suggests that these biomarkers hold significant diagnostic relevance and have the potential to open doors to novel treatment options.

How Probiotics help reduce inflammation in CKD- Restoring symbiosis in the gut microbiota may be a promising therapy for lowering inflammation and disease progression in CKD. Due to their ability to modulate the disrupted gut microbiota to a healthy eubiotic environment, probiotics significantly reduce inflammation and slow CKD progression. (1)

Role Of Probiotics in Reducing Inflammation through Enteric Dialysis:

• It is possible to decrease inflammation by supplementing the gut microbiota with probiotic bacteria, which digest nitrogenous waste products and other toxins that permeate the gut. (2) The procedure of introducing highly specialised strains of probiotic bacteria to digest different uremic toxins resulting from diminished kidney function is known as enteric dialysis. It also fights pathogenic bacteria using naturally released bacteriocins or antimicrobial peptides with antibiotic-like qualities, decreasing the production of toxic intermediate molecules and metabolites and improving the overall quality of life. (2)
• Probiotic supplementation appears to be associated with significant decreases in serum levels of proinflammatory cytokines (TNF-, IL-5, and IL-6 and endotoxins), as well as increased levels of anti-inflammatory cytokine (IL-10). Studies reveal preservation of residual renal function after six months of continuous oral supplementation with probiotics and a marked reduction of urea, creatinine, and potassium levels. (5)
• Lactobacillus and Bifidobacterium bacterial strains have been shown to reduce urea, blood urea nitrogen, ammonia levels, and plasma amounts of p-cresol and indoxyl sulfate in CKD patients. (6) Another advantage of these probiotic strains is that they help enhance Bifidobacteria populations (a genus known to have an essential role in the operation of the intestinal mucosal barrier), as well as lower cytokine and endotoxin concentrations and raise serum levels of IL-10. (6)
• Synbiotic supplementation may also have a favourable effect on the gut microbiota of CKD patients. A prescription of one synbiotic capsule per day for eight weeks increased Bifidobacterium and preserved Lactobacillus populations; supplementation for four weeks with probiotics (given three times a day) resulted in significant decreases in plasma p-cresol levels of patients with CKD stages 3 and 4, while supplementation with 15g a day of synbiotic probiotics resulted in effective reductions in serum p-cresol levels in patients with moderate to severe CKD. (7,8)
• Role of probiotics in maintaining e-GFR: With the ability to stabilise, maintain and improve GFR, probiotics offer a unique therapeutic opportunity to delay the progression of kidney failure. (2)
• Along these lines, a noteworthy study demonstrated that a probiotic supplement of L. acidophilus, Streptococcus thermophilus, and Bifidobacterium longum (taken for six months) has a positive impact on kidney function in various stages of CKD. The team elaborated that a 3.5 mL/ min/1.73 m² increase- translates to an 11.6% improvement in GFR, and 88% of survey respondents indicated that their quality of life improved drastically after being on the supplement. (2)

Key pointers-

• CKD is a chronic, progressive disease that raises the risk of developing life-threatening complications. This warrants an urgent need to control the disease in its initial stages by lowering the raised inflammatory markers associated with CKD.
• Probiotics reduce inflammation, improve kidney function and retard the progression of CKD by restoring the symbiosis of gut microflora in patients with CKD.
• Probiotic strains like L. acidophilus, S. thermophilus, and B. longum help to improve the GFR across different CKD stages, thus delaying the disease progression.

REFERENCES

1. Azim Sharaf El Din, U. A., Salem, M. M., &Abdulazim, D. O. (2016). Stop chronic kidney disease progression: Time is approaching. World Journal of Nephrology, 5(3), 258-273. https://doi.org/10.5527/wjn.v5.i3.258

2. Ranganathan N, Vyas U, Hanlon K, Ranganathan P, Irvin A, et al. (2018) Improvements in Glomerular Filtration Rate (GFR) in Chronic Kidney Disease (CKD) Patients Using a Commercial Patented and Proprietary Probiotic-Prebiotic Formulation* -3rd Biennial Survey. Int J Nephrol Kidney Fail 4(1): dx.doi.org/10.16966/2380-5498.154

3. Bello, A. K., Alrukhaimi, M., Ashuntantang, G. E., Basnet, S., Rotter, R. C., Douthat, W. G., Kazancioglu, R., Köttgen, A., Nangaku, M., Powe, N. R., White, S. L., Wheeler, D. C., & Moe, O. (2017). Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action. Kidney International Supplements, 7(2), 122-129. https://doi.org/10.1016/j.kisu.2017.07.007

4. Muslimovic, A., Rasic, S., Tulumovic, D., Hasanspahic, S., & Rebic, D. (2015). Inflammatory Markers and Procoagulants in Chronic Renal Disease Stages 1-4. Medical Archives, 69(5), 307-310. https://doi.org/10.5455/medarh.2015.69.307-310

5. Wang IK, Wu YY, Yang YF, Ting IW, Lin CC, Yen TH, et al. Probiotics' effect on cytokine and endotoxin serum levels in peritoneal dialysis patients: a randomized, double-blind, placebo-controlled trial. Benef Microbes. 2015;6:423–430

6. Bandeira Fagundes, R. A., Soder, T. F., Grokoski, K. C., Benetti, F., & Mendes, R. H. (2018). Probiotics in the treatment of chronic kidney disease: a systematic review. JornalBrasileiro de Nefrologia, 40(3), 278-286. https://doi.org/10.1590/2175-8239-JBN-3931

7. Guida B, Germanò R, Trio R, Russo D, Memoli B, Grumetto L, et al. Effect of short-term synbiotic treatment on plasma p-cresol levels in patients with chronic renal failure: a randomized clinical trial. NutrMetab Cardiovasc Dis. 2014;24:1043–1049.

8. Rossi M, Johnson DW, Morrison M, Pascoe EM, Coombes JS, Forbes JM, et al. Synbiotics Easing Renal Failure by Improving Gut Microbiology (SYNERGY): A Randomized Trial. Clin J Am Soc Nephrol. 2016;11:223–231.