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Table 1 Studies Regarding Relationship of Copeptin with Glomerular Filtration Rate Albuminuria/proteinuria and Clinical Outcomes

From: Pathophysiology of copeptin in kidney disease and hypertension

Study

With GFR

With Albuminuria/proteinuria

Subjects

Main Finding

Meijer et al. [43]

No data

No data

548 patients with renal transplantation

-Median follow-up was 3.2 years.

-Mean changes in eGFR during follow-up (3.2 yars) were -0.03, -0.44, and -1.06 mL/min/1.73 m2 per year (p:0.02) according to increasing copeptin tertiles

-In multivariate regression analysis, the association of copeptin with change in eGFR remained significant after adjustment

Meijer et al. [12]

Copeptin and eGFR were negatively associated (crude β:-0.17, P < 0.0001

Copeptin associated with UAE (R:0.20, P:0.001).

7593 participants with baseline urinary albumin concentration >10 mg/l

With increasing quintiles of copeptin levels, microalbuminuria increased from 13–25% in males and from 8–15% in females.

Meijer et al. [44]

Copeptin and eGFR were negatively asssociated (R:- 0.58, P < 0.0001)

Copeptin and albuminuria were positively asssociated R:0.39, P < 0.0001)

102 ADPKD patients

Copeptin was positively associated with renal volume R:0.47, P < 0.0001) and negatively with effective renal blood flow (R: -0.52, P < 0.0001)

Boertien et al. [45]

Copeptin and mGFR (inulin clearance) were inversely associated (std B:-0.258, P: 0.02)

No data

79 ADPKD subjects

-Patients who started RRT had higher copeptin levels compared to subjects who did not start RRT [4.10 (3.27–17.6) versus 2.27 (1.55-5.19) pmol/L, P:0.01]

Riphagen et al. [46]

eGFR decreased from 68 ± 14, 67 ± 15, 59 ± 18, as going copptin tertile 1 to tertile 3 (P < 0.0001)

ACR increased from 1.6 (0.9-4.0), 1.7 (0.8-6.1) 2.7 (1.0–8.2), as going copptin tertile 1 to tertile 3 (P < 0.0001)

1.195 patients with T2DM

-Log copeptin was associated with CV (HR 1.17 (95% CI 0.99-1.39); P:0.068) and all cause mortality (1.22 [1.09-1.36); P:0.001) after adjustment.

-However, copeptin did not substantially improve risk prediction for CV event (integrated discrimination improvement and all-cause mortality beyond currently used clinical markers.

Velho et al. [47]

Patients with highest tertile of co-peptin has lowest eGFR

Patients with highest tertile of co-peptin has Highest 24 h UAE

3.101 Type2DM patients with microalbuminuria (UAE, 20-200 mg/L) or macroalbuminuria (UAE > 200 mg/L) without renal failure at baseline

-The yearly variations of eGFR during follow-up by tertiles of plasma copeptin were 20.65 ± 0.24, 20.77 ± 0.24 and 21.91 ± 0.24 mL/min/1.73 m2 per year, respectively (ANCOVA P : 0.0001), adjusted for sex and age

-HR for plasma copeptin tertiles as a risk for renal events (defined as doubling of serum creatinine or development of end-stage renal disease) was 4.79 (95% CI, 2.48–9.24; P, 0.0001; for T3 vs. T1).

-This association remained significant when adjusted forbaseline UAE and eGFR 2.97 (1.56–6.14), P: 0.0006

Boertien et al, [48]

eGFR and baseline copeptin were negatively associated R: -0.143, P < 0.0001

logACR and baseline copeptin were positively associated R: 0.162, P < 0.0001

-1.328 patients with T2DM (349 (RAASi) and 979 without (RAASi)

-In multivarite analysis in 979 patients (without RAASi) baseline copeptin was associated with logACR; (β: 0.13, P < 0.001, and with eGFR, β −0.20, P < 0.001

-In 756 patients who were followed for 6.5 years baseline copeptin was not associated with increase in ACR after adjusment (β: 0.07, P:0.08) but associated with a decrease in eGFR ( β -0.09, P:0.03)

-There was no significant association between copeptin and change in ACR or eGFR in patients using RAASi at baseline.

Boertien et al. [49]

Baseline copeptin is correlated with mGFR, R:-0.286, P < 0.001

No data

-241 ADPKD patients with creatinine clearance >70 mL/min

-After a 8.5 (IQR, 7.7-9.0) years follow-up copeptin was significantly associated with change in TKV after adjusting for gender, age, cardiovascular risk factors and diuretic use (p = 0.03).

-Copeptin level was borderline significantly associated with change in mGFR after adjusting for these variables (p = 0.09).

Li et al. [50]

GFR and copeptin were inversely assocaited with (R:0.571, P < 0.001)

No data

86 non-dialysis patients with CKD and 20 control patients

-Among CKD patients, who had atherosclerotic plagues as measured by CIMT and left ventricular hypertrophy, had higher co-peptin levels compated to CKD patients without these pathologies.

-Elevated co-peptin was independently associated with GFR, left ventricular hypertrophy, CIMT and previous history of CVD in multivariate analysis.

Sontrop et al. [51]

Both at baseline (R:-0.53; P:0.003) and at 6 weeks follow-up, copeptin was inversely correlated with eGFR (R:-0.56;P:0.002)

-No correlation between copeptin and ACR at baseline.

-After 6 weeks a positive correlation was observed (r:0.44, P: 0.02)

28 patients with stage 3 CKD randomised to a hydration (to drink approximately 1 L more per day (n:17) than controls (n:11) for 6 weeks)

-In the hydration group, median copeptin decreased by 3.6 pmol/L, (P:0.005), while remaining stable among controls at 19 pmol/L (P:0.76).

Roussel et al. [52]

No data

No data

1.234 participants from the French general population with baseline co-peptin levels and followed for 9 years

Copeptin was associated with CKD according to KDIGO criterion: OR 3.03 (95% CI 1.21–7.57), P:0.02

Hu et al. [53]

Serum copeptin negatively related to GFR (R:-0.586, P < 0.001)

Co-peptin correlated with UAE (R:0.171, P:0.008)

120 T2DM patients

-Serum copeptin is an independent risk factor of decline in renal function in T2DM patients (OR:1.234, CI:1.003-1.456, p:0.012)

-Sensitivity and specificty of the co-peptin in detection of GFR decline by roc analysis were 78.9% and 88.9% respectively

Nakajima et al. [54]

No correlation between urinary co-peptin and eGFR

No data

50 patients with ADPKD

Urinary copeptin/u-Cr was associated with total kidney volume and height-adjusted total kidney volume in ADPKD

Ponte et al. [11]

-In both men and women eGFR is negatively associated with copeptin

Subjects with pathologic 24-h ACR had higher copeptin levels compared to subjects with normal ACR (5.0 pmol/L [IQR, 3.2–8.7] vs. 3.9 pmol/L [2.7–5.8];P:0.001).

Population based study of 529 women and 481 men

-Subjects with simple cysts had higher copeptin levels compared to patients without cysts (4.8 pmol/L [IQR, 3.6–7.9] versus 3.8 pmol/L [2.6–5.7]; P:0.001)

-The number of cysts in the kidneys is associated with copeptin

-In adjusted models, copeptin remained its association with CKD (OR, 2.82; 95% CI, 1.45 to 5.50; P:0.002) and ACR (OR, 1.70; 95% CI, 1.08 to 2.68; P:0.02

Tasevska et al. [3]

No data

No data

Derived from the population based MDCS

After multivariate adjustment copeptin was independently associated with significantly greater annual decline of eGFR according to the MDRD and CKD-EPI formula

Engelbertz et al. [5]

eGFR is lower in patients with elevated copeptin compared to patients with normal copeptin (41.4 vs. 70.1, P: 0.001)

Proteinuria was present in 35.8% of patients with elevated copeptin, but only in 15.5% of patients with normal copeptin (P < 0.001)

301 patients (35 had no CKD and the others have various degress of CKD) with an angiographically diagnosed stenosis ≥50%

During 180 days of follow-up, Multivariate Cox regression analysis showed that copeptin was the sole predictor for mortality (HR: 5.317 (95% CI 1.653-17.098, P = 0.005)

Schiel et al. [55]

Positive correlation between copeptin and GFR both in patients with type 1 diabetes (R:0.86, P: 0.021) and in healty controls (R: 0.61, P: 0.034).

No correlation with albuminuria

80 patients with type 1 diabetes and 61 healthy controls

In type 1 diabetic patients multivariate analyses showed that only GFR was associated with copeptin (β: 0.23, P:0.032). No independent association in healty controls

  1. GFR Glomerular Filtration Rate, eGFR estimated GFR, mGFR measured GFR, CKD Chronic kidney disease, CI Confidence Interval, HR Hazard Ratio, MDRD Modification of Diet in Renal Disease, CKD-EPI Chronic Kidney Disease Epidemiology Collaboration, ACR Albumin/creatinine ratio, T2DM Type 2 diabetes, MDCS Malmö Diet and Cancer Study, HD Hemodialysis, LV Left Ventricle, ROC Recieving operation Characterisitcs, ADPKD Autosomal dominant polycstic kidney disease, IQR interquartile range, uae Urinary Albumin Excretion, CV Cardiovascular, RAAS renin–angiotensin–aldosterone system, RAASi RAAS inhibition, RRT Renal replacement treatment, TKV Total Kidney Volume, CIMT Carotid Intima Media Thickness