INFLAMMATION STUDY UPDATES
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FINAL STUDY UPDATE
December 31, 2023
Dear Friends:
We received the final update to the study “Exploring the Role of Chronic Inflammation in the Pathogenesis of Feline Chronic Kidney Disease” from Principal Investigator Rosanne Jepson, BVSc (Dist), MVetMed, PhD, DipACVIM, DipECVIM, MRCVS., Professor at the Royal Veterinary College. Inflammation is known to be associated with CKD in humans; you will recall that, in this study, we endeavored to better understand the potential role of chronic inflammation in Feline CKD.
This study was seriously affected by the pandemic. There was an 18 month period where only emergency care could be provided, and even when this restriction was lifted, ongoing social distancing and sanitation protocols reduced the number and frequency of cats’ medical evaluations and care. The study period was extended for several months, but the hurdles and delays had some substantial and long-lasting effects; a significant number of cats enrolled in the study either dropped out, or passed away before full data regarding their conditions and care could be obtained, which affected data compilation and statistical analysis. Ongoing recruitment of cats for prospective portions of the study and biobanking of new blood samples* was also severely impacted.
I. INTRODUCTION
In this study, we prospectively analyzed cats’ ongoing medical conditions and care, and also retrospectively examined cats’ medical records, and biobanked blood samples, to investigate the relationships between inflammatory dental and periodontal diseases, specific inflammatory biomarkers**, and Feline CKD. For the retrospective portions, we had access to records and biobanked blood samples for 104 cats with azotemic CKD and 97 cats with non-azotemic CKD. For the prospective aspects, we had data from a maximum of 40 cats for analysis.
You will recall that our previously reported preliminary findings indicated that systemic chronic inflammation does indeed appear to be associated with Feline Chronic Kidney Disease. Furthermore, there does appear to be a significant association between the severity of dental and periodontal disease and markers of inflammation in cats with CKD. During this remainder of the study we endeavored to confirm the aforementioned findings, and to determine, in more specific detail, how and why these apparent associations exist, by looking at more specific relationships between inflammatory biomarkers and CKD in cats, within the context of dental and periodontal disease.
II. PERIODONTAL DISEASE AND THE DEVISED NOVEL DENTAL SCORING SYSTEM
You will recall that early on in the study, a novel dental scoring system was devised to analyze, photograph, and categorize the stage of dental and periodontal diseases based on the degree of tartar and gingivitis, with scores ranging from 1 to 4, with 4 representing the most severe pathology.
The pandemic substantially impacted enrollment and continuity, and resulted in a substantially lower number of cats being evaluated for oral photographic assessment coupled with available renal data than initially anticipated. We had planned to analyze a large number of cats prospectively based on CKD stage I (mildest) through IV (most severe)***, but because of the loss of so many cats in the study, we did not have enough cats at each individual CKD stage to do a meaningful analysis. Therefore, only comparisons between healthy senior cats, versus cats with CKD of varying stages were performed.
We found that tartar and gingivitis scores were overall higher in cats with CKD compared to cats without CKD, which could represent an association between periodontal disease and Feline CKD. But, since CKD tends to increase with aging, the association could also be purely or partly an indicator of a lack of good dental care generally over cats’ lifetimes, which is an ongoing serious problem in the domesticated feline population. Future studies with a larger cohort of cats could be beneficial, particularly if we can include age matched controls, and compare cats who have received quality dental care throughout their lifetime with those who have not been so fortunate.
An additional factor to consider is that there are some variables that can affect evaluations, including the possibility of some subjectivity on the part of the examiner despite identical training in the use of the scoring system, degree of cat compliance with exams, and loss of teeth, especially in older cats. Also, cats with darker pigmented gums are more difficult to assess for gingivitis.
III. RELATIONSHIP BETWEEN DENTAL DISEASE STATUS AND AZOTEMIC VERSUS NON-AZOTEMIC CKD STATUS
When CKD is advanced enough, waste products build up in the blood; this is known generally as azotemia. Non-azotemic CKD is generally milder, and can be diagnosed primarily by the presence and amount of protein in the urine. When non-azotemic cats and azotemic cats were grouped according to their dental disease status, cats with gingivitis were significantly more azotemic despite no significant differences in age between the two groups. This is the most significant finding in this segment of the study. Periodontal disease has been associated with CKD severity in humans and further study with age-matched controls in a larger cohort is warranted to explore this apparent association.
One thing that we can conclude with certainty is that a push needs to be made to raise awareness of the importance of regular feline dental care as a means of mitigating systemic disease.
IV. BIOMARKERS
Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state. CKD is notoriously difficult to detect; typically, by the time it’s discovered 70% of kidney function is lost. Some biomarkers, such as creatinine, are known to be associated with Chronic Kidney Disease. We investigated several inflammatory biomarkers which have a suspected association with kidney disease: Globulin, Albumin:Globulin ratio, SAA, and AGP. The goal is to understand existing biomarkers better, and to firmly establish new ones, so that we can develop a larger, better blood screening panel to aid in earlier detection of Feline CKD. One hundred four cats with azotemic CKD and 97 cats with non-azotemic CKD had their data included in this segment of the study.
A. Biomarkers and the Severity of Dental Disease
For this portion of the study, we examined the aforementioned biomarkers in concert with known indicators of Feline CKD, such as creatinine, both before and after periodontal treatment, to look for correlations:
1. There was a trend towards cats with more severe dental disease having a significantly lower albumin:globulin ratio as a consequence of higher globulin concentrations, which is suggestive of inflammation.
B. Associations Between Feline CKD, Dental Disease and Inflammatory Markers
Creatinine has a directly proportional relationship to CKD. We looked at the aforementioned biomarkers, as well as Packed Cell Volume, within the context of creatinine, dental disease and CKD to look for associations:
1. Cats in the azotemic group were identified as having a significantly higher proportion of advanced grade gingivitis (stage 2, 3 or 4) compared to the non-azotemic group.
2. There was a weak but significant negative correlation between creatinine and the biomarker SAA.
3. Neither the biomarkers SAA, AGP and A:G ratio, nor the grade of tartar and gingivitis demonstrated a relationship with progressive versus stable CKD.
C. Biomarkers in the Cats with Azotemic CKD
1. The Azotemic cats had significantly higher globulin concentrations, lower PCV, and significantly lower SAA concentrations. The higher proportion of cats with advanced grade gingivitis and tartar in the group of cats with azotemic CKD (referenced in B.1. above), potentially corresponds with the higher globulin concentration identified in these cats, which is suggestive of inflammation. This merits further investigation. It must be noted that the azotemic cats were significantly older, which is a potentially confounding variable--the increased prevalence of severe dental disease may be associated with aging, particularly in the absence of regular dental care.
2. In the cats with azotemic CKD, cats who had advanced CKD ie: IRIS stage 3 or 4 had significantly higher AGP and significantly lower PCV levels than cats at lower IRIS stages.
3. In the azotemic cats, weak negative correlations were identified between renal function assessed by creatinine concentration and SAA and PCV, but not with any other inflammatory markers.
4. In the azotemic cats, PCV was weakly positively correlated with both Albumin and A:G ratio, and very weakly positively correlated with globulin.
5. When evaluating cats with azotemic CKD, neither the biomarkers, nor the severity of periodontal disease differentiated between those identified to have stable versus progressive disease. Therefore, no specific link could be identified between dental disease severity and progression of renal disease.
D. Effects of Dental Procedures on Inflammatory Biomarkers
Utilizing retrospective analysis, prior to having dental procedures, 11 cats had been diagnosed with CKD (10 cats with IRIS Stage II and 1 cat with IRIS stage III) 3 cats with hyperthyroidism and CKD, and 5 cats had no existing conditions.
In this very small cohort, cats with IRIS Stage 2 CKD at the time of their dental procedure had a 25% increase in creatinine concentration. This is dramatic but, since the cohort was very small, It would be very beneficial to do a future prospective study with a larger cohort. Additionally, an expanded prospective study would allow for control and consideration of potential confounding variables that could affect outcomes, including peri-procedure and post-procedure blood pressure monitoring, concurrent fluid therapy, anesthesia details and pain medications and other concurrent and subsequent care factors, which may not have been available in this retrospective evaluation of existing medical records.
This prospective arm of this portion of the study was developed to evaluate cats for whom a dental procedure was recommended as part of their routine health care, to see whether or not dental procedures had an effect on CKD progression. In this very small cohort, the cats included were either healthy elderly cats, or cats with a prior diagnosis of CKD. No cats demonstrated new onset or progression of renal disease; there were no significant increases in renal parameters following their dental procedures. Further investigation with a much larger cohort is warranted; if our findings can be confirmed this would be great news for the future of safe dental care in cats with CKD.
We are proud of this research, and tremendously grateful to everyone who helped make this work possible. The fight for a feline CKD-free future continues, and we look forward to all that we will accomplish together.
* We will not fund any research that harms or exploits animals. Blood and urine samples utilized in this study are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the cats’ own necessary diagnostic purposes, were then preserved for use in this study with the consent of the cats’ human family members.
** Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
*** The International Renal Interest Society (IRIS) guidelines are considered the gold standard for staging and managing Feline CKD. Their staging of CKD ranges from Stage 1--the least advanced disease state, through Stage 4--the most advanced disease state.
Copyright 2023. Foundation For Feline Renal Research.
Dear Friends:
We received the final update to the study “Exploring the Role of Chronic Inflammation in the Pathogenesis of Feline Chronic Kidney Disease” from Principal Investigator Rosanne Jepson, BVSc (Dist), MVetMed, PhD, DipACVIM, DipECVIM, MRCVS., Professor at the Royal Veterinary College. Inflammation is known to be associated with CKD in humans; you will recall that, in this study, we endeavored to better understand the potential role of chronic inflammation in Feline CKD.
This study was seriously affected by the pandemic. There was an 18 month period where only emergency care could be provided, and even when this restriction was lifted, ongoing social distancing and sanitation protocols reduced the number and frequency of cats’ medical evaluations and care. The study period was extended for several months, but the hurdles and delays had some substantial and long-lasting effects; a significant number of cats enrolled in the study either dropped out, or passed away before full data regarding their conditions and care could be obtained, which affected data compilation and statistical analysis. Ongoing recruitment of cats for prospective portions of the study and biobanking of new blood samples* was also severely impacted.
I. INTRODUCTION
In this study, we prospectively analyzed cats’ ongoing medical conditions and care, and also retrospectively examined cats’ medical records, and biobanked blood samples, to investigate the relationships between inflammatory dental and periodontal diseases, specific inflammatory biomarkers**, and Feline CKD. For the retrospective portions, we had access to records and biobanked blood samples for 104 cats with azotemic CKD and 97 cats with non-azotemic CKD. For the prospective aspects, we had data from a maximum of 40 cats for analysis.
You will recall that our previously reported preliminary findings indicated that systemic chronic inflammation does indeed appear to be associated with Feline Chronic Kidney Disease. Furthermore, there does appear to be a significant association between the severity of dental and periodontal disease and markers of inflammation in cats with CKD. During this remainder of the study we endeavored to confirm the aforementioned findings, and to determine, in more specific detail, how and why these apparent associations exist, by looking at more specific relationships between inflammatory biomarkers and CKD in cats, within the context of dental and periodontal disease.
II. PERIODONTAL DISEASE AND THE DEVISED NOVEL DENTAL SCORING SYSTEM
You will recall that early on in the study, a novel dental scoring system was devised to analyze, photograph, and categorize the stage of dental and periodontal diseases based on the degree of tartar and gingivitis, with scores ranging from 1 to 4, with 4 representing the most severe pathology.
The pandemic substantially impacted enrollment and continuity, and resulted in a substantially lower number of cats being evaluated for oral photographic assessment coupled with available renal data than initially anticipated. We had planned to analyze a large number of cats prospectively based on CKD stage I (mildest) through IV (most severe)***, but because of the loss of so many cats in the study, we did not have enough cats at each individual CKD stage to do a meaningful analysis. Therefore, only comparisons between healthy senior cats, versus cats with CKD of varying stages were performed.
We found that tartar and gingivitis scores were overall higher in cats with CKD compared to cats without CKD, which could represent an association between periodontal disease and Feline CKD. But, since CKD tends to increase with aging, the association could also be purely or partly an indicator of a lack of good dental care generally over cats’ lifetimes, which is an ongoing serious problem in the domesticated feline population. Future studies with a larger cohort of cats could be beneficial, particularly if we can include age matched controls, and compare cats who have received quality dental care throughout their lifetime with those who have not been so fortunate.
An additional factor to consider is that there are some variables that can affect evaluations, including the possibility of some subjectivity on the part of the examiner despite identical training in the use of the scoring system, degree of cat compliance with exams, and loss of teeth, especially in older cats. Also, cats with darker pigmented gums are more difficult to assess for gingivitis.
III. RELATIONSHIP BETWEEN DENTAL DISEASE STATUS AND AZOTEMIC VERSUS NON-AZOTEMIC CKD STATUS
When CKD is advanced enough, waste products build up in the blood; this is known generally as azotemia. Non-azotemic CKD is generally milder, and can be diagnosed primarily by the presence and amount of protein in the urine. When non-azotemic cats and azotemic cats were grouped according to their dental disease status, cats with gingivitis were significantly more azotemic despite no significant differences in age between the two groups. This is the most significant finding in this segment of the study. Periodontal disease has been associated with CKD severity in humans and further study with age-matched controls in a larger cohort is warranted to explore this apparent association.
One thing that we can conclude with certainty is that a push needs to be made to raise awareness of the importance of regular feline dental care as a means of mitigating systemic disease.
IV. BIOMARKERS
Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state. CKD is notoriously difficult to detect; typically, by the time it’s discovered 70% of kidney function is lost. Some biomarkers, such as creatinine, are known to be associated with Chronic Kidney Disease. We investigated several inflammatory biomarkers which have a suspected association with kidney disease: Globulin, Albumin:Globulin ratio, SAA, and AGP. The goal is to understand existing biomarkers better, and to firmly establish new ones, so that we can develop a larger, better blood screening panel to aid in earlier detection of Feline CKD. One hundred four cats with azotemic CKD and 97 cats with non-azotemic CKD had their data included in this segment of the study.
A. Biomarkers and the Severity of Dental Disease
For this portion of the study, we examined the aforementioned biomarkers in concert with known indicators of Feline CKD, such as creatinine, both before and after periodontal treatment, to look for correlations:
1. There was a trend towards cats with more severe dental disease having a significantly lower albumin:globulin ratio as a consequence of higher globulin concentrations, which is suggestive of inflammation.
B. Associations Between Feline CKD, Dental Disease and Inflammatory Markers
Creatinine has a directly proportional relationship to CKD. We looked at the aforementioned biomarkers, as well as Packed Cell Volume, within the context of creatinine, dental disease and CKD to look for associations:
1. Cats in the azotemic group were identified as having a significantly higher proportion of advanced grade gingivitis (stage 2, 3 or 4) compared to the non-azotemic group.
2. There was a weak but significant negative correlation between creatinine and the biomarker SAA.
3. Neither the biomarkers SAA, AGP and A:G ratio, nor the grade of tartar and gingivitis demonstrated a relationship with progressive versus stable CKD.
C. Biomarkers in the Cats with Azotemic CKD
1. The Azotemic cats had significantly higher globulin concentrations, lower PCV, and significantly lower SAA concentrations. The higher proportion of cats with advanced grade gingivitis and tartar in the group of cats with azotemic CKD (referenced in B.1. above), potentially corresponds with the higher globulin concentration identified in these cats, which is suggestive of inflammation. This merits further investigation. It must be noted that the azotemic cats were significantly older, which is a potentially confounding variable--the increased prevalence of severe dental disease may be associated with aging, particularly in the absence of regular dental care.
2. In the cats with azotemic CKD, cats who had advanced CKD ie: IRIS stage 3 or 4 had significantly higher AGP and significantly lower PCV levels than cats at lower IRIS stages.
3. In the azotemic cats, weak negative correlations were identified between renal function assessed by creatinine concentration and SAA and PCV, but not with any other inflammatory markers.
4. In the azotemic cats, PCV was weakly positively correlated with both Albumin and A:G ratio, and very weakly positively correlated with globulin.
5. When evaluating cats with azotemic CKD, neither the biomarkers, nor the severity of periodontal disease differentiated between those identified to have stable versus progressive disease. Therefore, no specific link could be identified between dental disease severity and progression of renal disease.
D. Effects of Dental Procedures on Inflammatory Biomarkers
Utilizing retrospective analysis, prior to having dental procedures, 11 cats had been diagnosed with CKD (10 cats with IRIS Stage II and 1 cat with IRIS stage III) 3 cats with hyperthyroidism and CKD, and 5 cats had no existing conditions.
In this very small cohort, cats with IRIS Stage 2 CKD at the time of their dental procedure had a 25% increase in creatinine concentration. This is dramatic but, since the cohort was very small, It would be very beneficial to do a future prospective study with a larger cohort. Additionally, an expanded prospective study would allow for control and consideration of potential confounding variables that could affect outcomes, including peri-procedure and post-procedure blood pressure monitoring, concurrent fluid therapy, anesthesia details and pain medications and other concurrent and subsequent care factors, which may not have been available in this retrospective evaluation of existing medical records.
This prospective arm of this portion of the study was developed to evaluate cats for whom a dental procedure was recommended as part of their routine health care, to see whether or not dental procedures had an effect on CKD progression. In this very small cohort, the cats included were either healthy elderly cats, or cats with a prior diagnosis of CKD. No cats demonstrated new onset or progression of renal disease; there were no significant increases in renal parameters following their dental procedures. Further investigation with a much larger cohort is warranted; if our findings can be confirmed this would be great news for the future of safe dental care in cats with CKD.
We are proud of this research, and tremendously grateful to everyone who helped make this work possible. The fight for a feline CKD-free future continues, and we look forward to all that we will accomplish together.
* We will not fund any research that harms or exploits animals. Blood and urine samples utilized in this study are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the cats’ own necessary diagnostic purposes, were then preserved for use in this study with the consent of the cats’ human family members.
** Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
*** The International Renal Interest Society (IRIS) guidelines are considered the gold standard for staging and managing Feline CKD. Their staging of CKD ranges from Stage 1--the least advanced disease state, through Stage 4--the most advanced disease state.
Copyright 2023. Foundation For Feline Renal Research.
THIRD STUDY UPDATE
December 13, 2021
Dear Friends:
We are so grateful for the generous support you provide for Feline Chronic Kidney Disease research. You will recall that the goal of the above-referenced study, which is being conducted at The Royal Veterinary College, London, UK, is to better understand the potential role of chronic inflammation in Feline CKD. To that end, we’re examining various potential sources of inflammation, including dental disease and urinary tract infections, and how they may correlate with Feline CKD. We are also investigating inflammatory biomarkers* that could provide earlier warnings of Feline CKD development.
Although the pandemic continues to exert an effect, we are pleased to report that, since our last update, the study has continued to steadily improve and progress. The main clinic where we collect data, which had been seeing patients at a greatly reduced volume due to the pandemic, has increased the number of appointments. And the second clinic, which had been closed, has re-opened; it’s functioning at a slower pace than pre-pandemic due to continuing social distancing and sanitation measures, but the re-opening is a big step forward. There's also been some relaxing of restrictions in the laboratories; it's easier for the researchers to book time, which will help a great deal with getting the research back up to full speed.
Since the last update, here’s what we have accomplished:
Re: Dental Disease and Inflammation:
You will recall that the research team devised a dental disease scoring system, to provide consistency in assessing the nature and severity of dental disease, and to help provide consistency in evaluating its relationship to Feline CKD. The scoring system, having been established by the research team, has now been implemented with all clinicians in the main clinic. Additionally, to validate the study for clarity and consistency, 20 of the 32 cats who are currently included in this portion of the study will, with the permission of their human companions, have their dentition independently examined and scored by at least two different clinicians. To ensure that the scoring system is clear, and capable of yielding consistent results regardless of the clinician who is obtaining the data, this step is essential. The results obtained will be compared and analyzed, and the scoring system will be fine-tuned as necessary.
All cats have and will continue to receive a dental exam and scoring at each checkup for the duration of the study, and recruitment of additional cats for prospective dental scoring is ongoing. Additionally, you may recall from our previous update that there does appear to be correlation between specific dental pathology, certain inflammatory parameters, and kidney function parameters, but that we need to accrue a great deal more data to determine if these findings are significant and useful. To that end, we continue to recruit cats who present to the clinic with both CKD, and dental pathology requiring treatment.
Re: Biomarkers*:
One goal of this study is to evaluate several biomarkers that we suspect may be associated with Feline CKD, with the ultimate goal of creating a panel of biomarkers that will allow us to diagnose Feline CKD earlier. Candidates for the biomarker panel include inflammatory Serum Amyloid A (SAA), alpha-1 acid glycoprotein (AGP), Tumor Necrosis Factor-α, Interleukin-1, Interleukin-6 and Interleukin-8.
We have successfully amassed data on SAA and AGP thus far, and this data will be evaluated retrospectively in association with dental disease scoring to analyze for any associations between these markers and Feline CKD.
We have experienced a serious setback with regard to one type of biomarker, "cytokines”. Equipment required for studies can be very costly, which often results in research programs collaborating, so that equipment can be shared. Arrangements were made for collaboration between the Royal Veterinary College, London, UK, and Cornell University, NY, USA for cytokine analysis. Samples were shipped, frozen, from the RVC to Cornell, for data extraction utilizing equipment at Cornell, which would then be provided for analysis by the researchers at the RVC. The RVC took all proper steps for safe shipment, and Cornell was prepared to take prompt custody of the samples, and to keep them frozen for pending data extraction. Sadly, the samples were held by USA Customs for an extended time, for which they refused to provide any explanation. When the samples were finally released, they had defrosted. Cytokines are generally unstable at room-temperature and therefore, we will not be able to include retrospective evaluation of cytokines in association with dental disease as part of this study, and are working with the RVC to pursue a legal claim against USA Customs. Although we are deeply disappointed by this setback, it is, thankfully, only one aspect of this multifaceted project.
We are pleased to report that data for the biomarkers SAA and AGP has been collected for 120 cats with azotemic** CKD and 97 non-azotemic cats, and is being analyzed in association with retrospective dental scoring and CKD stage. Additional analysis will also include evaluation of associations between SAA and AGP and CKD progression and survival in the azotemic CKD cats, and development of CKD in the non-azotemic population. It is anticipated that this work will be completed by the end of January, 2022.
Re: Urinary Tract Infections:
Cats entering the clinic who are diagnosed with UTIs are managed and treated for their infections, and data has and will continue to be collected, to be analyzed for associations with Feline CKD.
Research requires patience and persistence, and science moves forward through thoughtful, evidence-based inquiry. Thank you so much for working with us towards a future where no cat knows the pain and suffering of kidney disease.
* Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
** Azotemia is a state wherein the urine contains waste products indicating that the kidneys, which usually eliminate these substances, are not working properly.
*** We will not fund any research that harms or exploits animals. The blood and urine samples being studied are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the necessary diagnostic purposes, were preserved for use in this study with the consent of the cats’ human family members.
Copyright 2021. Foundation For Feline Renal Research.
Dear Friends:
We are so grateful for the generous support you provide for Feline Chronic Kidney Disease research. You will recall that the goal of the above-referenced study, which is being conducted at The Royal Veterinary College, London, UK, is to better understand the potential role of chronic inflammation in Feline CKD. To that end, we’re examining various potential sources of inflammation, including dental disease and urinary tract infections, and how they may correlate with Feline CKD. We are also investigating inflammatory biomarkers* that could provide earlier warnings of Feline CKD development.
Although the pandemic continues to exert an effect, we are pleased to report that, since our last update, the study has continued to steadily improve and progress. The main clinic where we collect data, which had been seeing patients at a greatly reduced volume due to the pandemic, has increased the number of appointments. And the second clinic, which had been closed, has re-opened; it’s functioning at a slower pace than pre-pandemic due to continuing social distancing and sanitation measures, but the re-opening is a big step forward. There's also been some relaxing of restrictions in the laboratories; it's easier for the researchers to book time, which will help a great deal with getting the research back up to full speed.
Since the last update, here’s what we have accomplished:
Re: Dental Disease and Inflammation:
You will recall that the research team devised a dental disease scoring system, to provide consistency in assessing the nature and severity of dental disease, and to help provide consistency in evaluating its relationship to Feline CKD. The scoring system, having been established by the research team, has now been implemented with all clinicians in the main clinic. Additionally, to validate the study for clarity and consistency, 20 of the 32 cats who are currently included in this portion of the study will, with the permission of their human companions, have their dentition independently examined and scored by at least two different clinicians. To ensure that the scoring system is clear, and capable of yielding consistent results regardless of the clinician who is obtaining the data, this step is essential. The results obtained will be compared and analyzed, and the scoring system will be fine-tuned as necessary.
All cats have and will continue to receive a dental exam and scoring at each checkup for the duration of the study, and recruitment of additional cats for prospective dental scoring is ongoing. Additionally, you may recall from our previous update that there does appear to be correlation between specific dental pathology, certain inflammatory parameters, and kidney function parameters, but that we need to accrue a great deal more data to determine if these findings are significant and useful. To that end, we continue to recruit cats who present to the clinic with both CKD, and dental pathology requiring treatment.
Re: Biomarkers*:
One goal of this study is to evaluate several biomarkers that we suspect may be associated with Feline CKD, with the ultimate goal of creating a panel of biomarkers that will allow us to diagnose Feline CKD earlier. Candidates for the biomarker panel include inflammatory Serum Amyloid A (SAA), alpha-1 acid glycoprotein (AGP), Tumor Necrosis Factor-α, Interleukin-1, Interleukin-6 and Interleukin-8.
We have successfully amassed data on SAA and AGP thus far, and this data will be evaluated retrospectively in association with dental disease scoring to analyze for any associations between these markers and Feline CKD.
We have experienced a serious setback with regard to one type of biomarker, "cytokines”. Equipment required for studies can be very costly, which often results in research programs collaborating, so that equipment can be shared. Arrangements were made for collaboration between the Royal Veterinary College, London, UK, and Cornell University, NY, USA for cytokine analysis. Samples were shipped, frozen, from the RVC to Cornell, for data extraction utilizing equipment at Cornell, which would then be provided for analysis by the researchers at the RVC. The RVC took all proper steps for safe shipment, and Cornell was prepared to take prompt custody of the samples, and to keep them frozen for pending data extraction. Sadly, the samples were held by USA Customs for an extended time, for which they refused to provide any explanation. When the samples were finally released, they had defrosted. Cytokines are generally unstable at room-temperature and therefore, we will not be able to include retrospective evaluation of cytokines in association with dental disease as part of this study, and are working with the RVC to pursue a legal claim against USA Customs. Although we are deeply disappointed by this setback, it is, thankfully, only one aspect of this multifaceted project.
We are pleased to report that data for the biomarkers SAA and AGP has been collected for 120 cats with azotemic** CKD and 97 non-azotemic cats, and is being analyzed in association with retrospective dental scoring and CKD stage. Additional analysis will also include evaluation of associations between SAA and AGP and CKD progression and survival in the azotemic CKD cats, and development of CKD in the non-azotemic population. It is anticipated that this work will be completed by the end of January, 2022.
Re: Urinary Tract Infections:
Cats entering the clinic who are diagnosed with UTIs are managed and treated for their infections, and data has and will continue to be collected, to be analyzed for associations with Feline CKD.
Research requires patience and persistence, and science moves forward through thoughtful, evidence-based inquiry. Thank you so much for working with us towards a future where no cat knows the pain and suffering of kidney disease.
* Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
** Azotemia is a state wherein the urine contains waste products indicating that the kidneys, which usually eliminate these substances, are not working properly.
*** We will not fund any research that harms or exploits animals. The blood and urine samples being studied are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the necessary diagnostic purposes, were preserved for use in this study with the consent of the cats’ human family members.
Copyright 2021. Foundation For Feline Renal Research.
SECOND STUDY UPDATE
December 30, 2020
Dear Friends:
We hope this finds you safe and well. We're very grateful for the support you provide for Feline Chronic Kidney Disease research--this has been a tough year for everyone, and we can’t thank you enough for staying the course with us. Despite the pandemic, the battle against Feline CKD continues! Although the current inflammation study is moving at a significantly slower pace due to the pandemic, work remains underway, and we’re so thankful to the research team which, despite the current challenges, remain dedicated to the cause.
You will recall that the study goal is to better understand the potential role of chronic inflammation in Feline CKD. To that end, we’re examining various potential sources of inflammation, including dental disease and urinary tract infections, and how they may correlate with Feline CKD. We are also investigating inflammatory biomarkers* that could provide earlier warnings of Feline CKD development.
One positive development since the last update is that there does appear to be a correlation between specific dental pathology, such as gum recession and furcation involvement, certain inflammatory parameters, and kidney function parameters, including creatinine. This looks promising, but we must stress that we need to accrue a great deal more data to determine if these findings will be significant and useful.
Data collection and analysis for various aspects of this study, including the aforementioned dental disease research, have been hampered by the pandemic. This study has both retrospective and prospective aspects; both have been affected by the pandemic, with prospective work being more seriously affected. Retrospective work is performed when we look back, and analyze a set of data that has already been collected, such as when we examine previously bio-banked blood samples** and analyze them in concert with cats' existing clinical records to search for factors and data that may provide insights. Prospective data is collected going forward. The dental disease portion of this study is an example of prospective work: You’ll recall from a previous update that the research team developed a brand new scoring system to provide consistency and accuracy in analyzing the degree of dental disease, and to thereby create a database that will allow us to properly investigate correlations between degree and type of dental disease and Feline CKD. Each time a cat receives a dental exam, their data is contributed to the database with the goal being to build a new database of sufficient size and quality to provide statistically significant results.
In late March, at the beginning of the pandemic, the clinics and laboratories where data is collected, stored and analyzed were forced to close for all but emergency medical care. They reopened in July, but must operate more slowly and sparsely due to social distancing requirements and other safety and sanitization procedures. Despite these challenges, our commitment is unwavering. Work is proceeding as quickly as possible, and we hope that very soon, the battle against Feline CKD will proceed at full speed. We look forward to keeping you up to date on the critically important work you are helping make possible.
Research requires patience and persistence, and science moves forward through thoughtful, evidenced-based inquiry. Thank you so much for working with us towards a future where no cat knows the pain and suffering of kidney disease.
* Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
** We will not fund any research that harms or exploits animals. The blood and urine samples being studied are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the necessary diagnostic purposes, were preserved for use in this study with the consent of the cats’ human family members.
Copyright 2020. Foundation For Feline Renal Research.
Dear Friends:
We hope this finds you safe and well. We're very grateful for the support you provide for Feline Chronic Kidney Disease research--this has been a tough year for everyone, and we can’t thank you enough for staying the course with us. Despite the pandemic, the battle against Feline CKD continues! Although the current inflammation study is moving at a significantly slower pace due to the pandemic, work remains underway, and we’re so thankful to the research team which, despite the current challenges, remain dedicated to the cause.
You will recall that the study goal is to better understand the potential role of chronic inflammation in Feline CKD. To that end, we’re examining various potential sources of inflammation, including dental disease and urinary tract infections, and how they may correlate with Feline CKD. We are also investigating inflammatory biomarkers* that could provide earlier warnings of Feline CKD development.
One positive development since the last update is that there does appear to be a correlation between specific dental pathology, such as gum recession and furcation involvement, certain inflammatory parameters, and kidney function parameters, including creatinine. This looks promising, but we must stress that we need to accrue a great deal more data to determine if these findings will be significant and useful.
Data collection and analysis for various aspects of this study, including the aforementioned dental disease research, have been hampered by the pandemic. This study has both retrospective and prospective aspects; both have been affected by the pandemic, with prospective work being more seriously affected. Retrospective work is performed when we look back, and analyze a set of data that has already been collected, such as when we examine previously bio-banked blood samples** and analyze them in concert with cats' existing clinical records to search for factors and data that may provide insights. Prospective data is collected going forward. The dental disease portion of this study is an example of prospective work: You’ll recall from a previous update that the research team developed a brand new scoring system to provide consistency and accuracy in analyzing the degree of dental disease, and to thereby create a database that will allow us to properly investigate correlations between degree and type of dental disease and Feline CKD. Each time a cat receives a dental exam, their data is contributed to the database with the goal being to build a new database of sufficient size and quality to provide statistically significant results.
In late March, at the beginning of the pandemic, the clinics and laboratories where data is collected, stored and analyzed were forced to close for all but emergency medical care. They reopened in July, but must operate more slowly and sparsely due to social distancing requirements and other safety and sanitization procedures. Despite these challenges, our commitment is unwavering. Work is proceeding as quickly as possible, and we hope that very soon, the battle against Feline CKD will proceed at full speed. We look forward to keeping you up to date on the critically important work you are helping make possible.
Research requires patience and persistence, and science moves forward through thoughtful, evidenced-based inquiry. Thank you so much for working with us towards a future where no cat knows the pain and suffering of kidney disease.
* Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
** We will not fund any research that harms or exploits animals. The blood and urine samples being studied are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the necessary diagnostic purposes, were preserved for use in this study with the consent of the cats’ human family members.
Copyright 2020. Foundation For Feline Renal Research.
FIRST STUDY UPDATE
December 21, 2019
Dear Friends:
We’ve received the latest update to the study “Exploring the Role of Chronic Inflammation in the Pathogenesis of Feline Chronic Kidney Disease” from Principal Investigator Rosanne Jepson, BVSc (Dist), MVetMed, PhD, DipACVIM, DipECVIM, MRCVS. You will recall that, in this study we will endeavor to better understand the potential role of chronic inflammation in Feline CKD.
The first year of this three-year long study is complete. Here is what we have accomplished:
I. A retrospective review of cats’ medical records and their corresponding bio-banked blood samples*, to select cats for inclusion in the study has been performed, and;
II. A subsequent detailed examination of those records and samples has been performed to determine:
A. If chronic inflammation is, generally, associated with Feline CKD;
B. If chronic inflammation corresponds with dental disease in cats and;
C. If dental disease is associated with CKD in cats.
Based on their records and their existing CKD status, 538 cats were selected for inclusion in the study, with kidney health conditions ranging from non-azotemic (no demonstrable signs of CKD), to IRIS stage 4 **CKD.
Our preliminary findings at this early stage indicate that systemic chronic inflammation does indeed appear to be associated with Feline Chronic Kidney Disease. Furthermore, there does appear to be a significant association between inflammation in cats with CKD and the severity of dental disease.
We must now dig deeper. During the remainder of the study we will endeavor to confirm the aforementioned findings, and will attempt to determine, in more specific detail, how and why there appears to be an association between inflammation and CKD in cats. We will do this by looking at specific biomarkers*** of systemic and renal inflammation. One important goal of this study is to establish an optimal panel of biomarkers that could be used in the future to determine a cat’s risk of developing CKD, and/or to diagnose CKD at an earlier stage by measuring the levels of these biomarkers in the blood. We will also work to obtain more specific information into the relationship between dental disease and inflammation and, ultimately, between dental disease and CKD. To this end, a scoring system has been devised to categorize the stage of dental disease based on the degree of tartar and gingivitis. Scores range from 1 to 4, with 4 representing the most severe pathology, and each cat seen for a checkup will have the results of their oral examination carefully documented with a score and photographs.
Additional highlights of upcoming work on this study include prospective evaluation of the relationship between dental disease and urinary tract infections on chronic inflammation and CKD, and how treatment of these conditions may affect chronic inflammation and/or kidney function.
Research requires patience and persistence, and science moves forward through thoughtful, evidence-based inquiry. The process is neither quick nor simple; thank you very much for standing with us in the battle against Feline CKD. We look forward to providing you with an additional update soon.
* We will not fund any research that harms or exploits animals. Blood and urine samples utilized in this study are routine samples provided by companion cats during the course of their regularly scheduled veterinary visits. The samples, after being used for the cats’ own necessary diagnostic purposes, are then preserved for use in this study with the consent of the cats’ human family members.
** The International Renal Interest Society’s (IRIS’) guidelines are considered the gold standard for staging and managing Feline CKD. Their staging of CKD ranges from Stage 1--the least advanced disease state, through Stage 4—the most advanced disease state.
*** Biomarkers are physical characteristics that can be measured--for example, particular proteins circulating in blood, that can be signs of an abnormal or diseased state.
Copyright 2019. Foundation For Feline Renal Research.
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We care passionately about animal welfare issues, and about feline kidney disease in particular, but please understand that we are not veterinarians, and are not qualified to provide veterinary medical advice. If you have a companion animal suffering from kidney disease it is imperative that you consult with a licensed veterinarian, who is qualified to provide you with medical advice and care that meets your animal’s particular health needs.
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