Cardiology Research, ISSN 1923-2829 print, 1923-2837 online, Open Access
Article copyright, the authors; Journal compilation copyright, Cardiol Res and Elmer Press Inc
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Original Article

Volume 17, Number 5, October 2026, pages 437-452


Dual Antioxidant Supplementation With N-Acetylcysteine and Taurine (Nefrosave®) for Cardio-Renal Protection in Chronic Kidney Disease Patients With Diabetes and/or Hypertension: A Real-World, Retrospective, Comparative Study

Figures

↓  Figure 1. Median comparison between NAC + taurine plus standard of care versus standard of care alone from baseline to 12 ± 2 weeks for (a) change in uACR (mg/g), (b) change in serum creatinine (mg/dL), and (c) change in eGFR (mL/min/1.73 m2). NAC: N-acetylcysteine; uACR: albumin-to-creatinine ratio; eGFR: estimated glomerular filtration rate.
Figure 1.
↓  Figure 2. Median comparison between NAC + taurine plus standard of care versus standard of care alone from baseline to 12 ± 2 weeks stratified by CKD stages for change in uACR (mg/g). NAC: N-acetylcysteine; uACR: albumin-to-creatinine ratio; CKD: chronic kidney disease. Level of significance, *P < 0.05, ***P < 0.001.
Figure 2.
↓  Figure 3. Median comparison between NAC + taurine plus standard of care versus standard of care alone from baseline to 12 ± 2 weeks stratified by CKD stages for change in serum creatinine (mg/dL). NAC: N-acetylcysteine; CKD: chronic kidney disease. Level of significance, *P < 0.05, ***P < 0.001.
Figure 3.
↓  Figure 4. Median comparison between NAC + taurine plus standard of care versus standard of care alone from baseline to 12 ± 2 weeks stratified by CKD stages for change in eGFR (mL/min/1.73 m2). NAC: N-acetylcysteine; CKD: chronic kidney disease; eGFR: estimated glomerular filtration rate. Level of significance, *P < 0.05, ***P < 0.001.
Figure 4.
↓  Figure 5. Proportions of patients with ≥ 30% improvement in uACR and serum creatinine from baseline to 12 ± 2 weeks. uACR: urinary albumin-to-creatinine ratio. Level of significance, *P < 0.05, **P < 0.01.
Figure 5.

Tables

↓  Table 1. Baseline Demographics and Clinical Characteristics
 
ParametersNAC + taurine + standard of careStandard of careP-value
*P < 0.05, **P < 0.01, and ***P < 0.001. NAC: N-acetylcysteine; SD: standard deviation; CKD: chronic kidney disease; SPO2: oxygen saturation; NA: not available.
Overall patients, n300150-
Age (years), mean ± SD59.79 ± 12.3056.53 ± 13.800.017*
Weight (kg), mean ± SD68.22 ± 9.6368.77 ± 8.590.374
Height (cm), mean ± SD165.74 ± 7.55166.01 ± 7.330.998
Sex0.999
  Male, n (%)196 (65.33%)98 (65.33%)
  Female, n (%)104 (34.67%)52 (34.67%)
Stage of CKD0.006**
  Stage 1, n (%)16 (5.33%)19 (12.67%)
  Stage 2, n (%)61 (20.33%)33 (22.00%)0.682
  Stage 3, n (%)223 (74.33%)98 (65.33%)0.047*
Systolic blood pressure (SBP) (mm Hg), mean ± SD137.93 ± 16.53141.39 ± 12.900.010*
Diastolic blood pressure (DBP) (mm Hg), mean ± SD84.48 ± 7.9785.85 ± 5.810.185
Pulse rate (beats per minute), mean ± SD78.32 ± 6.5077.01 ± 5.660.042*
SPO2 (%)0.07
  n7130
  Mean ± SD96.31 ± 0.7196.60 ± 0.89
Temperature (°F)0.25
  n119
  Mean ± SD97.91 ± 0.4897.70 ± 0.36
Respiratory rate (breaths per minute)0.301
  n1111
  Mean ± SD19.82 ± 2.2720.64 ± 2.50
Duration of CKD (years)0.999
  Number of patients with CKD (%)300 (100%)150 (100%)
  Mean ± SD3.11 ± 2.761.93 ± 1.31< 0.001***
Duration of hypertension (years)0.027*
  Number of patients with hypertension (%)270 (90.00%)144 (96.00%)< 0.001***
  Mean ± SD9.56 ± 9.117.08 ± 9.46
Duration of type 2 diabetes mellitus (T2DM) (years)
  Number of patients with T2DM (%)188 (62.67%)57 (38.00%)< 0.001***
  Mean ± SD9.92 ± 9.1011.67 ± 11.470.944
Both hypertension and type 2 diabetes mellitus, n (%)158 (52.67%)51 (34.00%)< 0.001***
Alcohol status
  Non-drinker259 (86.33%)130 (86.67%)0.922
  Quit drinking26 (8.67%)10 (6.67%)0.461
  Casual drinking5 (1.67%)4 (2.67%)0.619
  Occasional drinker7 (2.33%)6 (4.00%)0.320
  Social drinker3 (1.00%)-NA
Smoking status
  Non-smoker244 (81.33%)120 (80.00%)0.735
  Quit smoking51 (17.00%)20 (13.33%)0.315
  Casual smoking1 (0.33%)1 (0.33%)0.499
  Moderate smoking1 (0.33%)2 (1.33%)0.248
  Light smoking3 (1.00%)6 (4.00%)0.243
  Chain smoker-1 (0.67%)NA

 

↓  Table 2. Change in uACR (mg/g) Stratified by CKD Stages From Baseline to 12 ± 2 Weeks of Treatment in the Two Groups
 
Baseline12 ± 2 weeksMean difference from baseline to 12 ± 2 weeks, Δ (Δ%) (95% CI), P-value###Adjusted mean difference from baseline to 12 ± 2 weeks, δ (95% CI), P-value#Median of difference from baseline to 12 ± 2 weeks (95% CI), P-value##
Statistical tests used: #Mann−Whitney U test; ##Wilcoxon signed-rank test; ###repeated-measures ANOVA; ***repeated-measures ANCOVA; between-group difference: univariate ANCOVA; level of significance, P < 0.001. uACR: urinary albumin-to-creatinine ratio; CI: confidence interval; NAC: N-acetylcysteine; SD: standard deviation; CKD: chronic kidney disease; Q1, Q3: first and third quartiles; ANOVA: repeated-measures analysis of variance; ANCOVA: repeated-measures analysis of covariance; min, max: minimum, maximum.
Overall
NAC + taurine + standard of care (n = 300)
  Mean ± SD, µg/mg159.87 ± 65.37146.11 ± 64.89−13.76 (−8.61%),
(−15.27, −12.26),
< 0.001***
−13.76 (−15.25, −12.27),
< 0.001***
−12.40 (−14.00, −10.80),
< 0.001***
  Median (min, max)160.05 (30.00, 298.05)140.00 (27.00, 295.60)
  Q1, Q3104.00, 203.9790.62, 199.90
Standard of care (n = 150)18.68 (11.26%)
(16.54, 20.81),
< 0.001***
18.67 (16.50, 20.84),
< 0.001***
18.10 (16.63, 19.66),
< 0.001***
  Mean ± SD, µg/mg165.85 ± 58.71184.53 ± 58.64
  Median (min, max)178.30 (36.00, 294.56)199.35 (39.00, 298.10)
  Q1, Q3108.60, 207.59130.00, 224.71
  Between-group difference−32.44 (−35.05, −29.83),
< 0.001***
−33.01 (−35.74, −30.28),
< 0.001***
−30.34 (−32.60, −28.00),
< 0.001***
Stage 1 CKD
NAC + taurine + standard of care (n = 16)
  Mean ± SD, µg/mg146.16 ± 54.77117.75 ± 59.70−28.41 (−19.44%)
(−33.71, −23.11),
< 0.001***
−24.11 (−33.74, −14.49),
< 0.001***
−28.11 (−35.35, −21.89),
< 0.001***
  Median (min, max)144.10 (85.00, 284.88)110.15 (50.10, 280.00)
  Q1, Q398.50, 179.6566.28, 150.52
Standard of care (n = 19)24.85 (19.75%)
(19.98, 29.71),
< 0.001***
21.23 (12.90, 29.57),
< 0.001***
24.31 (20.21, 29.39),
< 0.001***
  Mean ± SD, µg/mg125.84 ± 31.58150.69 ± 33.86
  Median (min, max)121.67 (88.50, 198.54)140.14 (109.80, 220.36)
  Q1, Q3102.04, 148.30122.98, 180.10
  Between-group difference−53.26 (−60.45, −46.06),
< 0.001***
−45.65 (−62.46, −28.84),
< 0.001***
−52.55 (−61.00, −45.20),
< 0.001***
Stage 2 CKD
NAC + taurine + standard of care (n = 61)
  Mean ± SD, µg/mg155.61 ± 49.98131.18 ± 46.86−24.43 (−15.70%)
(−27.99, −20.87),
< 0.001***
−25.05 (−28.72, −21.38),
< 0.001***
−23.11 (−27.00, −19.69),
< 0.001***
  Median (min, max)156.87 (44.00, 280.10)124.00 (30.00, 250.16)
  Q1, Q3114.65, 185.5694.47, 154.35
Standard of care (n = 33)19.91 (10.77%)
(15.07, 24.75),
< 0.001***
21.05 (15.76, 26.35),
< 0.001***
19.41 (15.22, 23.29),
< 0.001***
  Mean ± SD, µg/mg184.89 ± 59.13204.80 ± 57.25
  Median (min, max)191.28 (94.60, 288.30)210.40 (120.00, 298.00)
  Q1, Q3120.00, 222.36130.50, 245.55
  Between-group difference−44.34 (−50.36, −38.34),
< 0.001***
−48.46 (−55.70, −41.22),
< 0.001***
−42.28 (−48.46, −37.00),
< 0.001***
Stage 3 CKD
NAC + taurine + standard of care (n = 223)
  Mean ± SD, µg/mg162.02 ± 69.68152.22 ± 68.42−9.80 (−6.05%)
(−11.32, −8.27),
< 0.001***
−9.42 (−10.93, −7.90),
< 0.001***
−8.78 (−10.17, −7.52),
< 0.001***
  Median (min, max)166.10 (30.00, 298.05)150.00 (27.00, 295.60)
  Q1, Q3104.00, 208.9096.00, 202.20
Standard of care (n = 98)17.06 (10.20%)
(14.77, 19.36),
< 0.001***
16.21 (13.87, 18.55),
< 0.001***
16.52 (15.00, 18.26),
< 0.001***
  Mean ± SD, µg/mg167.20 ± 59.31184.26 ± 60.20
  Median (min, max)186.78 (36.00, 294.56)200.10 (39.00, 298.10)
  Q1, Q3107.00, 208.09121.15, 226.62
  Between-group difference−26.86 (−29.62, −24.10),
< 0.001***
−26.08 (−28.97, −23.18),
< 0.001***
−25.22 (−27.58, −23.04),
< 0.001***

 

↓  Table 3. Change in Serum Creatinine (mg/dL) Stratified by CKD Stages From Baseline to 12 ± 2 Weeks of Treatment in the Two Groups
 
Baseline12 ± 2 weeksMedian of difference from baseline to 12 ± 2 weeks (95% CI), P-value##Median of difference between groups (95% CI), P-value#
Statistical tests used: #Mann–Whitney U test; ##Wilcoxon signed-rank test; level of significance, ***P < 0.001. CI: confidence interval; NAC: N-acetylcysteine; SD: standard deviation; CKD: chronic kidney disease; Q1, Q3: first and third quartiles; min, max: minimum, maximum.
Overall
NAC + taurine + standard of care (n = 300)−0.05 (−0.06, −0.05),
< 0.001***
−0.20 (−0.20, −0.20),
< 0.001***
  Mean ± SD, mg/dL1.54 ± 0.381.46 ± 0.43
  Median (min, max)1.54 (0.56, 2.44)1.50 (0.30, 2.40)
  Q1, Q31.30, 1.801.20, 1.70
Standard of care (n = 150)0.15 (0.11, 0.15),
< 0.001***
  Mean ± SD, mg/dL1.47 ± 0.371.60 ± 0.35
  Median (min, max)1.40 (0.80, 2.40)1.60 (0.80, 2.40)
  Q1, Q31.20, 1.731.40, 1.90
Stage 1 CKD
NAC + taurine + standard of care (n = 16)−0.20 (−0.29, −0.09),
0.001**
−0.36 (−0.48, −0.26),
< 0.001***
  Mean ± SD, mg/dL0.85 ± 0.120.66 ± 0.19
  Median (min, max)0.90 (0.56, 1.00)0.69 (0.40, 1.00)
  Q1, Q30.80, 0.910.50, 0.82
Standard of care (n = 19)2.00 (0.15, 2.50),
< 0.001***
  Mean ± SD, mg/dL1.01 ± 0.111.19 ± 0.16
  Median (min, max)1.10 (0.80, 1.10)1.20 (0.80, 1.40)
  Q1, Q30.90, 1.101.10, 1.30
Stage 2 CKD
NAC + taurine + standard of care (n = 61)−0.13 (−0.18, −0.10),
< 0.001***
−0.30 (−0.35, −0.21),
< 0.001***
  Mean ± SD, mg/dL1.16 ± 0.211.00 ± 0.28
  Median (min, max)1.20 (0.80, 1.60)1.00 (0.30, 1.50)
  Q1, Q30.98, 1.310.80, 1.20
Standard of care (n = 33)0.15 (0.12, 0.20),
< 0.001***
  Mean ± SD, mg/dL1.16 ± 0.161.33 ± 0.20
  Median (min, max)1.20 (0.80, 1.40)1.40 (1.00, 1.70)
  Q1, Q31.10, 1.301.10, 1.50
Stage 3 CKD
NAC + taurine + standard of care (n = 223)−0.05 (−0.05, −0.03),
< 0.001***
−0.17 (−0.20, −0.13),
< 0.001***
  Mean ± SD, mg/dL1.69 ± 0.291.65 ± 0.30
  Median (min, max)1.70 (1.08, 2.44)1.60 (1.00, 2.40)
  Q1, Q31.50, 1.891.40, 1.80
Standard of care (n = 98)0.11 (0.10, 0.14),
< 0.001***
  Mean ± SD, mg/dL1.66 ± 0.301.78 ± 0.28
  Median (min, max)1.60 (1.10, 2.40)1.80 (1.10, 2.40)
  Q1, Q31.40, 1.891.58, 2.00

 

↓  Table 4. Change in eGFR (mL/min/1.73 m2) Stratified by CKD Stages From Baseline to 12 ± 2 Weeks of Treatment in the Two Groups
 
Baseline12 ± 2 weeksMedian of difference from baseline to 12 ± 2 weeks (95% CI), P-value##Median of difference between groups (95% CI), P-value#
Statistical tests used: #Mann–Whitney U test; ##Wilcoxon signed-rank test; level of significance, ***P < 0.001. eGFR: estimated glomerular filtration rate; CI: confidence interval; NAC: N-acetylcysteine; SD: standard deviation; CKD: chronic kidney disease; Q1, Q3: first and third quartiles; min, max: minimum, maximum.
Overall
NAC + taurine + standard of care (n = 300)2.06 (1.60, 2.71),
< 0.001***
7.51 (6.52, 8.92),
< 0.001***
  Mean ± SD, mL/min/1.73 m250.62 ± 17.1954.97 ± 22.42
  Median (min, max)46.00 (30.00, 106.00)47.59 (30.13, 130.60)
  Q1, Q338.00, 60.7540.03, 62.95
Standard of care (n = 150)−5.47 (−6.75, −4.54),
< 0.001***
  Mean ± SD, mL/min/1.73 m255.30 ± 19.1848.62 ± 15.24
  Median (min, max)49.00 (30.00, 99.00)44.24 (28.39, 93.19)
  Q1, Q341.00, 68.0036.96, 57.95
Stage 1 CKD
NAC + taurine + standard of care (n = 16)10.05 (3.97, 17.20),
< 0.001***
25.97 (19.89, 33.65),
< 0.001***
  Mean ± SD, mL/min/1.73 m297.00 ± 4.62108.07 ± 11.81
  Median (min, max)96.00 (91.00, 106.00)107.12 (93.68, 130.60)
  Q1, Q392.50, 101.2596.13, 117.04
Standard of care (n = 19)
  Mean ± SD, mL/min/1.73 m293.00 ± 2.3876.92 ± 8.02−17.40 (−20.56, −11.73),
< 0.001***
  Median (min, max)93.00 (90.00, 99.00)74.39 (66.53, 93.19)
  Q1, Q391.00, 95.0070.63, 84.05
Stage 2 CKD
NAC + taurine + standard of care (n = 61)9.96 (7.33, 13.44),
< 0.001***
19.67 (16.00, 24.20),
< 0.001***
  Mean ± SD, mL/min/1.73 m269.34 ± 7.8781.56 ± 16.79
  Median (min, max)66.00 (60.00, 86.00)77.43 (58.37, 128.35)
  Q1, Q362.00, 76.5067.37, 92.98
Standard of care (n = 33)−10.22 (−12.70, −7.76),
< 0.001***
  Mean ± SD, mL/min/1.73 m268.94 ± 6.3458.71 ± 8.39
  Median (min, max)69.00 (61.00, 86.00)58.24 (44.38, 83.84)
  Q1, Q364.00, 71.5053.18, 62.32
Stage 3 CKD
NAC + taurine + standard of care (n = 223)1.26 (0.98, 1.51),
< 0.001***
11.39 (9.58, 12.79),
< 0.001***
  Mean ± SD, mL/min/1.73 m242.17 ± 7.5443.89 ± 8.40
  Median (min, max)42.00 (30.00, 59.00)42.83 (30.13, 70.87)
  Q1, Q336.00, 48.0037.15, 49.77
Standard of care (n = 98)−3.47 (−4.07, −2.95),
< 0.001***
  Mean ± SD, mL/min/1.73 m243.40 ± 8.1439.73 ± 7.08
  Median (min, max)43.00 (30.00, 59.00)38.67 (28.39, 57.88)
  Q1, Q337.00, 49.0034.90, 44.08