Normoalbuminuric CKd Presentation journal club

Journal club presentation on NACKD

1. Prevalence of Normoalbuminuric Chronic Kidney Disease Among Individuals with Type 2 Diabetes Mellitus from India Moderator : Dr Syeda Ayesha, Dr Vaishak Presented by: Dr D keerti

2. Introduction Diabetes mellitus is a leading cause of chronic kidney disease (CKD) And ESRD requiring renal replacement therapy In a patient with diabetes there is 30-40%( 50-60% ) risk of nephropathy Rate of fall of GFR in DKD is 8-10ml/min/yea r

3. Traditional markers: albuminuria and low eGFR But growing evidence indicates that a substantial proportion of patients either with type 1 diabetes or type 2 diabetes have renal function loss without out overt proteinuria, or have renal function loss even with normoalbuminuria

4. Definition of CKD CKD is defined as abnormalities of kidney structure or function, present for ≥3 months, with implications for health ( either of the following present for 3 months ) Markers of Kidney Damage Albuminuria > 30 mg/day Urine sediment abnormalities (e.g., hematuria, red cell casts etc) Electrolyte and other abnormalities due to tubular disorders.

5. Abnormalities detected by histology Structural abnormalities detected by imaging History of kidney transplantation Decreased GFR <60 mL/min/ 1.73 m2

6. Pathogenesis of DKD

7. If renal autoregulation is maintained hyper infiltration will not lead to intraglomerular hypertension but In diabetes there is alteration of signal transduction of afferent arteriolar: impaired renal autoregulation Proteins are tubulotoxic which are endocytosed( clathrin and megalin )by the tubules and leads to inflammation and fibrosis

8. Potential mechanisms of NADKD • Aging-related kidney changes, including nephrosclerosis. • Effective glycemic and blood pressure control with multidisciplinary therapies. • Use of renin-angiotensin system blockades, reducing proteinuria but not preventing CKD progression. • Possible role of tubular damage in progression, as indicated by biomarkers like KIM-1 and TNF pathways.

9. NADKD is a heterogeneous disease with extremely complex pathogenesis, which may involve genetic factors , vascular lesions (more macroangiopathy than microangiopathy) glomerular lesions , intrarenal arteriosclerosis , mild forms of tubular injury ,acute kidney injury , inflammation , metabolic syndrome , obesity , hypertension , hyperlipidemia , hyperuricemia

10. Diagnosis of NACKD the diagnosis of NADKD should meet at least the following condition 1) diagnosis of DM according to WHO or the American Diabetes Association (ADA) 2) diagnosis of CKD according to KADIGO 3) examination once a month and at least twice in three months if AER<30 mg/24 h or ACR<30 mg/g is diagnosed as NADKD

11. Bio markers Neutrophil gelatinase-associated lipocalin Cystatin C Fatty acid-binding protein Vascular endothelial growth factor

12. Renal prognosis and mortality NA DKD generally has a lower risk of progression to advanced CKD or ESRD compared to proteinuric DKD. • Annual eGFR decline is slower in NADKD patients: - ~1.9 mL/min/1.73 m² for compared to 3.0–3.3 mL/min/1.73 m² for proteinuric DKD. • Mortality rates are lower for NACKD compared to proteinuric DKD.

13. In this study Prevalence of normoalbuminuric chronic kidney disease among individuals with type 2 diabetes mellitus from India Published on: Indian Journal Med Research , October & November 2022, pp 632-639 Done by: Chellamma Jayakumari, Ramesh Gomez, Sasidharan Dipin Et al

14. BACKGROUND OF STUDY A subset of diabetic individuals are known to develop progressive renal insufficiency without albuminuria, referred to as normoalbuminuric chronic kidney disease (NACKD). There is, however, a paucity of studies regarding this condition in India. So, this study, aimed to find the prevalence of normoalbuminuric renal dysfunction and its clinical associations in diabetic Indian population.

15. Objectives Primary Objective: To determine the prevalence of NACKD among Indian patients with type 2 diabetes mellitus (T2DM). Secondary Objective: To explore clinical and biochemical associations of NACKD . Discuss potential mechanisms and implications of NADKD.

16. Study Design Type : Retrospective observational stud y Location : Indian Institute of Diabetes, Thiruvananthapura Duration : June 2017 – January 2020

17. Inclusion Criteria: Newly registered T2DM patients with complete clinical and biochemical data. Exclusion Criteria: Chronic infections, liver disease, severe thyroid dysfunction, active/recurrent UTIs. Sample Size: Initial screening: 3,615 Final sample: 3,534 after exclusions.

18. Methods Data Collection: Medical records for demographics, comorbidities, medications, and lab results. Analysis Tools: SPSS v25 for statistical analysis.

19. Classification : 1. No Kidney Disease (NKD) 2. Albuminuria Alone (ALB) 3. Normoalbuminuric CKD (NACKD) 4. Albuminuric CKD (ACKD)

20. Key Results Prevalence : Data from 3534 diabetes patients with NACKD constituted 39.1 per cent of the patients with reduced e-GFR, NACKD was found in 2.1 per cent and ACKD in 3.4 per cent of all diabetic patients.

21. Risk Factors: NACKD: Higher age, male sex, lower body weight, statin use. No significant association with glycemic parameters (HbA1c, FBG, PPBG).

22. Discussion Comparative Findings: NACKD vs ACKD: Higher proportion of NACKD patients were males (70.6%) when compared to those with NKD (59.2%). NACKD: Higher age, lower BMI, fewer retinopathy cases. Significantly higher number of subjects with NACKD was on statins and ACEI/ARBs when compared to those with NKD.

23. Macrovascular complications were comparable in both groups. Retinopathy and Hypertension was found to be more prevalent in the ACKD patients It was found that NACKD patients had a significantly lower duration of diabetes, lower body weight, lower systolic and diastolic blood pressures, lower fasting (FPG) and postprandial (PPPG) plasma glucose and lower HbA1c levels when compared to ACKD

24. - NACKD decreases with advanced CKD stages (45% in stage 3A, 10% in stages 4/5).

25. Limitations • Retrospective study design limits causality assessment. • Single-center study: potential referral bias. • Lack of detailed follow-up or repeat measurements of albuminuria.

26. Conclusion NACKD accounts for over one-third of CKD cases in T2DM. Strong associations with age and male sex but not with hyperglycemia. NADKD represents a clinically and pathologically heterogeneous phenotype of DKD. Further studies are needed to identify biomarkers and develop targeted therapies for NADKD Understanding NADKD can enhance personalized treatment for diabetic kidney disease.

27. References Harrisson Brenner and Rectors KDIGO guidelines Related studies

28. Thank you