Effectiveness of Subgingival Instrumentation on Delaying End-stage Renal Diseases Among Chronic Kidney Disease Patients

Effectiveness of Subgingival Instrumentation on Delaying End-stage Renal Diseases Among Chronic Kidney Disease Patients: A Non-Randomized Clinical Study

Chronic kidney disease (CKD) and periodontitis share a bidirectional inflammatory relationship, with cytokines such as IL-6, TNF-α, and hsCRP driving progression in both conditions. Non-surgical periodontal therapy (NSPT) has shown reductions in systemic inflammatory markers with emerging evidence of improved renal function, yet robust Randomized controlled trials targeting pre-dialysis Stage IV-V diabetic CKD patients remain lacking. In the Indian context, where diabetes-related CKD is rapidly rising and access to dialysis is limited, there is a clear lacuna in literature regarding the effectiveness of NSPT in delaying progression to end-stage renal disease. Hence, the present Randomized controlled trial is undertaken to address this gap.

Study Overview

• Status: Not yet recruiting
• Conditions: Periodontitis; Chronic Kidney Disease; End Stage Renal Disease (ESRD)
• Intervention / Treatment: Procedure: Subgingival Instrumentation; Other: Oral Hygiene Instructions

Detailed Description

Chronic kidney disease (CKD) is a major socio-economic and healthcare problem and represents a significant global public health challenge. The burden of disease is disproportionately higher in low- and middle-income countries. As per the Global Burden of Disease (GBD) 2023 estimates, approximately 788 million people were affected by CKD globally, with a global age-adjusted prevalence of 14.2% among adults aged 20 years and older. CKD has a significant global burden, affecting over 9% of the world population and was directly responsible for 1.2 million deaths worldwide in 2017 alone.

Chronic kidney disease is defined as the presence of kidney damage or an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m² persisting for three months or more, irrespective of the underlying cause. It represents a state of progressive loss of kidney function, ultimately resulting in the need for renal replacement therapy in the form of dialysis or kidney transplantation. Kidney damage refers to pathological abnormalities detected by imaging or renal biopsy, abnormalities in urinary sediment, or increased urinary albumin excretion rates.

The leading cause of CKD is diabetes mellitus, followed by hypertension and glomerular diseases. The prevalence of individuals with CKD due to type 1 diabetes has continued to increase globally, rising by 21.7% between 2007 and 2017 and reaching approximately 3.2 million individuals in 2017. These individuals are at increased risk of cardiovascular complications, and nearly 25-30% progress to kidney failure. Irrespective of the initial nephropathy, once a critical mass of nephrons is lost, kidney disease generally follows a progressive course toward advanced stages, resulting in increased morbidity and mortality.

The burden of CKD arises not only from the management of end-stage kidney disease but also from complications related to CKD and its associated comorbidities. There are effective strategies to reduce the rate of CKD progression and improve patient outcomes; therefore, the need for therapies aimed at slowing disease progression is critical.

Periodontal bacteria, which cause chronic inflammation and the breakdown of tooth-supporting structures, are the cause of periodontal disease, a chronic infectious oral illness. One of the most prevalent oral illnesses worldwide is periodontitis, affecting almost 20-50% of the global population in varying degrees, and the percentage rises with advancing age. In India, 51% of people had periodontal disease overall. Periodontal disease is implicated as an independent risk factor for CKD. Periodontitis is defined as an inflammatory disease of the supporting tissues of the teeth caused by specific microorganisms or groups of microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone, with periodontal pocket formation, gingival recession, or both.

Chronic kidney disease and periodontal disease are strongly interconnected through shared inflammatory, metabolic, and immune pathways. Periodontal disease has been implicated as an independent risk factor for CKD and may also act as a risk factor for several acquired systemic diseases. The bidirectional relationship between periodontal disease and systemic conditions highlights the importance of oral health assessment in medically compromised populations.

Inflammation is defined as the tissue's biological response to harmful stimuli such as pathogens or irritants. Chronic inflammation and elevated inflammatory markers play a crucial role in the progression and adverse outcomes of CKD. Evidence from previous studies demonstrates that declining renal function is associated with increased levels of circulating inflammatory cytokines. Several investigations have proposed that chronic dental infections, particularly periodontal disease, contribute significantly to the systemic inflammatory burden observed in CKD patients. The pathophysiological concept of periodontitis involves the systemic dissemination of inflammatory mediators such as CRP, IL-6, and tumor necrosis factor-α (TNF-α), either due to local bacterial infection causing periodontal tissue destruction or through the systemic spread of periodontal pathogens and their endotoxins. Periodontitis, being a chronic inflammatory condition, may significantly amplify the existing systemic inflammatory burden in CKD, thereby contributing to disease progression and associated complications.

Periodontal infections worsen the systemic inflammatory status, leading to poor renal outcomes in CKD patients. Improving oral health care through Non Surgical Periodontal Thearpy may improve the systemic inflammatory status and improve renal function. Various studies demonstrated elevated levels of CRP and IL-6 in patients with periodontal disease and their significant reduction following non-surgical periodontal therapy (NSPT). These findings suggest that periodontal intervention may play a role in modulating systemic inflammation.

In the Indian context, where the prevalence of diabetes and CKD is increasing rapidly and access to dialysis remains limited for a large proportion of the population, strategies aimed at delaying progression to end-stage renal disease are of particular importance. Oral health is often neglected in medically compromised individuals, and periodontal disease frequently remains untreated. Addressing periodontal health may therefore represent an overlooked yet impactful component of comprehensive CKD care.

Thus, the present Non- Randomized controlled study is designed to evaluate the effectiveness of subgingival instrumentation in delaying the progression to end-stage renal disease or the initiation of dialysis among diabetic patients with stage IV-V chronic kidney disease. By assessing both periodontal and renal parameters over a defined follow-up period of 12 months, this study aims to generate evidence supporting the integration of periodontal care into the comprehensive management of diabetic CKD patients.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Gurleen Kaur, MDS; Phone Number: +91 9354031553; Email: drgurleenphd@gmail.com
• Study Contact Backup: Name: Vipul Yadav, MDS; Phone Number: +91 8826363961; Email: vipulyadavv.97@gmail.com

Study Locations

• India
  • Haryana
    • Rohtak, Haryana, India, 124001
      • Post Graduate Institute of Dental Sciences , Rohtak
      • Contact: Gurleen Kaur, MDS; Phone Number: 9354031553; Email: drgurleenphd@gmail.com
      • Contact: Vipul Yadav, MDS; Phone Number: 8826363961; Email: vipulyadavv.97@gmail.com
      • Principal Investigator: Gurleen Kaur, MDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients aged 40-70 years.
• Type 2 diabetes mellitus with chronic kidney diseases and currently on oral hypoglycemic agents.
• Diagnosed with Stage IV or V (eGFR between 15-20 mL/min/1.73m²).
• Not undergoing dialysis.
• Presence of ≥20 natural teeth.
• Diagnosed with moderate (Stage II) (as per 2017 World Workshop classification) (Interdental CAL at site of greatest loss >2mm but <5 mm in ≥ 2 non- adjacent teeth).
• Willingness to provide written informed consent.

Exclusion Criteria:

• Patients already undergoing hemodialysis or renal transplantation.
• Patients on insulin therapy or taking SGLT2 inhibitors and GLP-1 receptor agonist.
• HbA1c level >8 %.
• Any Periodontal therapy within past 6 months.
• Immunocompromised patients.
• Any history of tobacco use.
• Pregnant or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; IG participants will receive subgingival instrumentation using an ultrasonic scaler (NSK Variose 2 Ultrasonic Scaler) and hand instruments (Sickle scalers and Curettes, GDC) followed by oral hygiene instructions (OHI).	Procedure: Subgingival Instrumentation; Participants will receive subgingival instrumentation using an ultrasonic scaler (NSK Variose 2 Ultrasonic Scaler) and hand instruments (Sickle scalers and Curettes, GDC) followed by oral hygiene instructions (OHI).; Other: Oral Hygiene Instructions; Participants will receive basic oral hygiene instructions
Active Comparator: Comparator Group; control group participant will receive basic oral hygiene instructions	Other: Oral Hygiene Instructions; Participants will receive basic oral hygiene instructions

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated Glomerular filtration rate	Renal function will be assessed by calculating the Estimated Glomerular filtration rate (eGFR) using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The CKD-EPI equation incorporates serum creatinine concentration, age, and sex to provide an estimate of kidney function expressed as mL/min/1.73 m².	Estimated Glomerular filtration rate (eGFR) estimation will be performed at 3,6,9 and 12 months
Soluble Urokinase Plasminogen Activator Receptor(suPAR)	The estimation of soluble urokinase plasminogen activator receptor (suPAR) in plasma will be performed using a sandwich Enzyme-Linked Immunosorbent Assay (ELISA). The assay employs a sandwich ELISA technique, where suPAR in the plasma sample binds to specific antibodies immobilized on the microplate. Following incubation and washing steps, an enzyme-conjugated detection antibody and substrate solution will be added. The enzymatic reaction produced a measurable color change proportional to the concentration of suPAR. The absorbance will be recorded at 450 nm using an ELISA microplate reader, and the concentration was calculated using a standard curve.	The estimation of soluble urokinase plasminogen activator receptor (suPAR) will be done at baseline and 12 months.
Periodontal markers	Different periodontal markers including Pocket Probing Depth(PPD) , Clinical Attachment Loss(CAL), Bleeding on Probing(BOP), Calculus Component of Oral Hygiene Index will be estimated. Measurement will be done six sites (mesiobuccal, mid-buccal, distobuccal, mesiolingual/palatal, mid-lingual/palatal, and distolingual/palatal) on all maxillary and mandibular teeth. PPD will be measured from the gingival margin to the base of the pocket, while CAL will be measured from the CEJ to the base of the pocket/sulcus. All the measurements will be rounded to the nearest millimeter and were recorded using a Williams probe. For BOP, WHO Probe will be used and bleeding areas are documented at six sites per tooth.	Measurement will be done at Baseline, 3, 6, 9 and 12 months.
Renal parameters including Serum Creatinine, Serum albumin and Serum urea	Renal parameters including Serum Creatinine, Serum albumin and Serum urea will be assessed. Serum creatinine levels will be estimated using the Jaffe's kinetic method / enzymatic colorimetric method on an automated biochemistry analyser. The results will be expressed in milligrams per decilitre (mg/dL). Serum albumin levels will be measured using the bromocresol green (BCG) dye-binding method. The results were expressed in grams per decilitre (g/dL). The normal reference range for serum albumin was taken as 3.5-5.0 g/dL. Serum urea will be estimated using the urease-glutamate dehydrogenase (GLDH) method / diacetyl monoxime method on an automated analyser. The values will be expressed in mg/dL, with a normal reference range of 15-45 mg/dL.	Renal parameters including Serum Creatinine, Serum albumin and Serum urea will be assessed at baseline,3,6,9 and 12 months.
Percentage of Chronic Kidney Disease patients progressing from pre-dialysis to dialysis.	Percentage of Chronic Kidney Disease patients progressing from pre-dialysis to dialysis will be calculated.	Percentage of Chronic Kidney Disease patients progressing from pre-dialysis to dialysis will be estimated from baseline till 12 month follow up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High-sensitivity C-reactive protein (hs-CRP)	The concentration of high-sensitivity C-reactive protein (hs-CRP) in plasma will be estimated using a high-sensitivity immunoturbidimetric assay with a commercially available diagnostic kit. Plasma sample will be added to hs-CRP reagent containing anti-CRP antibodies. The mixture will be incubated to allow antigen-antibody complex formation. The change in absorbance will be measured using an automated biochemical analyzer. hs-CRP concentration will be determined using a calibration curve.	Change in High-sensitivity C-reactive protein (hs-CRP) levels from baseline to 3,6,9 and 12 months will be checked.
Glycated Haemoglobin (HbA1c) levels	Glycated haemoglobin (HbA1c) levels will be measured to assess long-term glycaemic control among study participants. Venous blood samples will be collected and analyzed using standardized laboratory methods. HbA1c reflects the average blood glucose concentration over the preceding 2-3 months and will be expressed as a percentage (%). The measured HbA1c values will be used to evaluate participants' glycemic status. Assessment will be performed at baseline, 3, 6, 9 and 12 months.	Glycated haemoglobin (HbA1c) levels assessment will be done at baseline, 3, 6, 9 and 12 months.

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Dental Sciences Rohtak
• Investigators: Study Director: Vipul Yadav, MDS, Professor, Department of Public Health Dentistry, Post Graduate Institute of Dental Sciences Rohtak

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 3, 2026
• First Submitted That Met QC Criteria: June 3, 2026
• First Posted (Actual): June 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: End Stage Renal Disease; Chronic Kidney Disease; Periodontitis; Dialysis; Subgingival Instrumentation
• Additional Relevant MeSH Terms: Urogenital Diseases; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Periodontitis; Kidney Failure, Chronic; Renal Insufficiency, Chronic
• Other Study ID Numbers: Gurleen2676

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No