Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

Zittema, Debbie; Berg, Else van den; Meijer, Esther; Boertien, Wendy E.; Kobold, Anneke C. Muller; Franssen, Casper F. M.; Jong, Paul E. de; Bakker, Stephan J. L.; Navis, Gerjan; Gansevoort, Ron T.

doi:10.2215/cjn.08690813

Cited by 42 publications

(28 citation statements)

References 29 publications

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“…In addition, in type 2 diabetes patients treated in primary healthcare, increased levels of copeptin were associated with elevated risk of cardiovascular and all-cause mortality [10], findings in line with 2 of our own previous studies showing strong independent association between copeptin and cardiovascular morbidity and mortality, especially in patients with diabetes [11,12]. In healthy kidney donors, eGFR decreased significantly following donation but copeptin remained unchanged, suggesting that AVP, as measured by copeptin, may in fact be causally related to the decline of eGFR rather than just being a small molecule marker of eGFR [13]. Here, we investigated if copeptin independently predicts decline of eGFR and development of chronic kidney disease (CKD) in a large population-based study.…”

Section: Introductionsupporting

confidence: 80%

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Tasevska¹,

Enhörning²,

Christensson³

et al. 2016

Am J Nephrol

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Background: Our aim was to test if plasma copeptin, a stable surrogate marker of arginine vasopressin, predicts decline of glomerular filtration rate (GFR) and risk of chronic kidney disease (CKD). Methods: We measured copeptin and renal function at the Malmö Diet and Cancer Cardiovascular Cohort baseline exam and reassessed renal function after a follow-up time of 16.6 ± 1.5 years (n = 3,186). Furthermore, we defined CKD based on an estimated GFR (eGFR) calculated by the Modification of Diet in Renal Disease (MDRD) <60 (CKD_60_MDRD), <45 (CKD_45_MDRD) and <30 (CKD_30_MDRD) ml/min/1.73 m². Results: After multivariate adjustment (gender, age, baseline eGFR, smoking status, systolic blood pressure, antihypertensive treatment and follow-up time), copeptin (beta-coefficient per 1 SD increment of copeptin) was independently associated with significantly greater annual decline of eGFR (ml/min/1.73 m²) according to the MDRD formula (OR 0.057, 95% CI 0.022-0.093; p = 0.001) as well as according to the CKD Epidemiology Collaboration (CKD-EPI) formula (OR 0.050, 95% CI 0.022-0.077; p < 0.001). Each SD increment of copeptin independently predicted incident CKD_60_MDRD (OR 1.19, 95% CI 1.04-1.36; p = 0.010), CKD_45_MDRD (OR 1.33, 95% CI 1.04-1.71; p = 0.026) and CKD_30_MDRD (OR 3.69, 95% CI 1.41-9.66; p = 0.008). The relationship between copeptin and CKD defined by CKD-EPI gave similar results. Conclusion: Our data suggest that increased levels of copeptin independently predict decline in eGFR and greater risk of new-onset CKD.

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Section: Introductionsupporting

confidence: 80%

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Tasevska¹,

Enhörning²,

Christensson³

et al. 2016

Am J Nephrol

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“…Recent experimental and epidemiological findings have renewed the interest in the components of the water balance and in the parameters reflecting this integrative function [1,4,9,18,22,24,28,29,32,42,43]. It is indeed quite different for the kidney to excrete a daily osmolar load of 900 mosm in 1 L of urine at 900 mosm/L or in 3 L of urine at 300 mosm/L.…”

Section: Discussionmentioning

confidence: 99%

“…They include the specific urine density (UD) or the refraction index that give only an approximate value of the solute content in the urine and are subjected to several biases including distortion in the case of proteinuria and poor precision of readings. Two other surrogates are the urine concentrating index (UCI) based on the handling of creatinine by the kidney [30,31], and the estimated U osm (eU osm ) based on the concentration of the 3 main osmoles present in the urine: sodium, potassium, and urea [31,32]. To our knowledge, the validity of these 2 surrogates has not been evaluated in large, population-based cohorts with normal or altered renal function.…”

Section: Introductionmentioning

confidence: 99%

Validation of Surrogates of Urine Osmolality in Population Studies

et al. 2017

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Background: The importance of vasopressin and/or urine concentration in various kidney, cardiovascular, and metabolic diseases has been emphasized recently. Due to technical constraints, urine osmolality (U_osm), a direct reflect of urinary concentrating activity, is rarely measured in epidemiologic studies. Methods: We analyzed 2 possible surrogates of U_osm in 4 large population-based cohorts (total n = 4,247) and in patients with chronic kidney disease (CKD, n = 146). An estimated U_osm (eU_osm) based on the concentrations of sodium, potassium, and urea, and a urine concentrating index (UCI) based on the ratio of creatinine concentrations in urine and plasma were compared to the measured U_osm (mU_osm). Results: eU_osm is an excellent surrogate of mU_osm, with a highly significant linear relationship and values within 5% of mU_osm (r = 0.99 or 0.98 in each population cohort). Bland-Altman plots show a good agreement between eU_osm and mU_osm with mean differences between the 2 variables within ±24 mmol/L. This was verified in men and women, in day and night urine samples, and in CKD patients. The relationship of UCI with mU_osm is also significant but is not linear and exhibits more dispersed values. Moreover, the latter index is no longer representative of mU_osm in patients with CKD as it declines much more quickly with declining glomerular filtration rate than mU_osm. Conclusion: The eU_osm is a valid marker of urine concentration in population-based and CKD cohorts. The UCI can provide an estimate of urine concentration when no other measurement is available, but should be used only in subjects with normal renal function.

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“…99–101 Plasma levels of copeptin, a surrogate for vasopressin, have also been found to be elevated in ADPKD patients compared to healthy individuals after donation of a kidney for transplantation despite higher glomerular filtration rate (GFR) in the ADPKD patients. 102 Furthermore, plasma copetin levels have been shown to correlate with the severity of PKD in cross-sectional studies and with the rate of disease progression in prospective studies. 103–105 The cause of the elevated levels of vasopressin and copeptin is thought to be impaired urinary-concentrating capacity, which is one of the earliest if not the earliest manifestation of ADPKD and can be detected in patients with normal glomerular filtration rate and even in children with ADPKD.…”

Section: Introductionmentioning

confidence: 99%

Vasopressin and disruption of calcium signalling in polycystic kidney disease

et al. 2015

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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common monogenic kidney disease and the fourth leading cause of end-stage renal disease, responsible for 5–10% of cases. The disease is characterized by relentless development and growth of cysts causing progressive kidney enlargement associated with hypertension, pain, reduced quality of life, and eventually kidney failure. It is caused by mutations to PKD1 or PKD2, encoding polycystin-1 and polycystin-2, respectively. Their function and the molecular mechanisms responsible for the development of polycystic kidney disease are not well understood. The objective of this review is to synthesize a large body of literature that examines how reduction of functional PC1 or PC2 at the primary cilia and/or the endoplasmic reticulum directly disrupts intracellular calcium signaling and indirectly disrupts calcium regulated cAMP and purinergic signaling. We propose a hypothetical model where dysregulated metabolism of cAMP and purinergic signaling increase the sensitivity of principal cells in collecting ducts and of tubular epithelial cells in the distal nephron to the constant tonic action of vasopressin. The resulting magnified response to vasopressin further enhances the disruption of calcium signaling initiated by mutations to PC1 or PC2 and activates downstream signaling pathways responsible for impaired tubulogenesis, cell proliferation, increased fluid secretion and interstitial inflammation.

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Kidney Function and Plasma Copeptin Levels in Healthy Kidney Donors and Autosomal Dominant Polycystic Kidney Disease Patients

Cited by 42 publications

References 29 publications

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Increased Levels of Copeptin, a Surrogate Marker of Arginine Vasopressin, Are Associated with an Increased Risk of Chronic Kidney Disease in a General Population

Validation of Surrogates of Urine Osmolality in Population Studies

Vasopressin and disruption of calcium signalling in polycystic kidney disease

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