Comparative Effect of Normal Protein and Low Protein Diet on Renal Function Reserve in Patients of Chronic Kidney Disease Stage 3 And 4: A Randomised Controlled Study

Background: Renal functional reserve (RFR), defined as the difference between peak and baseline glomerular filtration rate (GFR), reflects the adaptive capacity of the kidney. This study evaluated how normal protein diet (NPD) and low protein diet (LPD) affect changes in both absolute (RFR _abs ) and relative (RFR _% ) RFR, as well as rate of GFR decline over six months in patients with CKD stages 3 and 4. Methodology: This six‑month randomized controlled trial enrolled adults (>18 years) with stage 3–4 CKD. Baseline assessments included clinical and laboratory parameters, eGFR, Creatinine clearance (CrCl) and two‑plasma technetium-99m Diethylenetriamine pentaacetic acid ( ^99m Tc‑DTPA) method before and after a 1 g/kg protein load to calculate RFR _abs and RFR _% . Patients were randomized to either a normal protein diet (0.8 g/kg/day) or a low protein diet (0.6 g/kg/day). Dietary adherence monitored by recall, record and 24‑hour urinary urea nitrogen. All parameters were repeated at six months to compare RFR _abs and RFR _% changes by both measured GFR methods between diet groups. Patients having RFR below median value of the study population were considered to have low renal reserve; risk factors of low RFR were also assessed. Results: Of 135 patients (64 NPD, 71 LPD), there was significant increase in measured GFR after protein loading in both groups at baseline and at six months (p < 0.001). The magnitude of increase in GFR after protein loading didn’t differ between groups at baseline (p = 0.88), but significantly high in LPD group at six months (p = 0.03). The decline in RFR was significantly smaller in LPD than NPD after six months by both the methods of RFR estimation (RFR _abs (DTPA): p = 0.002; RFR _% (DTPA): p = 0.001 and RFR _abs (CrCl): p=0.046; RFR _% (CrCl): p=0.021; respectively), with no significant difference in eGFR change between groups. Lower baseline GFR, higher proteinuria and increased age were independent risk factors for low renal reserve. Conclusion: LPD preserved both absolute and relative RFR compared to NPD. Decline in RFR preceded fall in GFR, making it a potential early biomarker for CKD progression. Trial registration: - Clinical Trial Registry (India) CTRI – CTRI/2024/08/071864 dated 2 ^nd August 2024 Key words: Chronic kidney disease, creatinine clearance, technetium-99m Diethylenetriamine pentaacetic acid, low protein diet, normal protein diet, renal function reserve