Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function

Azurmendi, Pablo Javier; Fraga, Adriana; Galan, Felicita; Kotliar, C.; Arrizurieta, Elvira; Valdez, Marta G.; Forcada, Pedro; Stefan, Jose S. Santelha; Martín, Roció Belén

doi:10.1093/ndt/gfp136

Cited by 25 publications

(22 citation statements)

References 26 publications

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“…Azurmendi et al showed that even modest increases in albuminuria in adults with ADPKD are associated with subtle markers of renal (urine monocyte chemoattractant protein-1 levels) and vascular (carotid intima-media thickness) damage [33]. Seventeen (36%) of patients were found to have microalbuminuria at the last follow-up, and this was comparable in both groups.…”

Section: Discussionmentioning

confidence: 99%

Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms

2010

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Autosomal dominant polycystic kidney disease (ADPKD) in children is sometimes considered to be a benign condition, with morbidity manifesting in adulthood. Therefore, diagnostic screening of children at risk is controversial. The aim of our study was to to compare the manifestations of ADPKD in children diagnosed by postnatal ultrasound (US) screening versus those presenting with symptoms. This was a retrospective chart review of children with ADPKD assessed in a single centre between 1987 and 2007. Age and reason for diagnosis were noted, and children were separated into two groups: (1) those diagnosed on the basis of family-based screening; (2) those presenting with a symptom. The two groups were compared for renal size, number of cysts, estimated glomerular filtration rate (eGFR), the presence of hypertension and microalbuminuria. In the 47 children with ADPKD (21 females) from 33 families who satisfied the enrollment criteria, mean (standard deviation) age at referral and last follow-up was 7.2 (4.4) and 12.9 (5.1) years, respectively, and the mean follow-up duration was 5.7 (3.6) years. Diagnosis was based on postnatal US screening in 31 children, whereas 16 were diagnosed after presenting with symptoms. The proportions of children with nephromegaly, hypertension, microalbuminuria and decreased eGFR, respectively, were similar in both groups. Based on these results, we conclude that renal-related morbidities, including hypertension and microalbuminia, do occur in children with ADPKD and at a similar frequency in those diagnosed after presenting with symptoms and those diagnosed upon postnatal screening. We suggest that at-risk children should have regular checks to detect hypertension. Moreover, affected children may benefit from novel therapies to minimise cystic disease progression.

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Section: Discussionmentioning

confidence: 99%

Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms

2010

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“…Cultured epithelial cells from human ADPKD cysts produce an array of chemokines and cytokines that have the potential to induce inflammation and interstitial matrix remodelling. In patients with ADPKD some of these cytokines and chemokines are excreted in the urine at levels above normal 25–27 . Moreover, renal cysts in animals with mutations in PKD1 orthologues also produce inflammatory chemo kines, supporting the notion that the interstitial changes observed in ADPKD are secondary to the production of inflammatory factors by renal cyst epithelial cells 28,29 .…”

Section: The Pathogenesis Of Cyst Formationmentioning

confidence: 99%

The importance of total kidney volume in evaluating progression of polycystic kidney disease

2016

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The rate at which autosomal dominant polycystic kidney disease (ADPKD) progresses to end-stage renal disease varies widely and is determined by genetic and non-genetic factors. The ability to determine the prognosis of children and young adults with ADPKD is important for the effective life-long management of the disease and to enable the efficacy of emerging therapies to be determined. Total kidney volume (TKV) reflects the sum volume of hundreds of individual cysts with potentially devastating effects on renal function. The sequential measurement of TKV has been advanced as a dynamic biomarker of disease progression, yet doubt remains among nephrologists and regulatory agencies as to its usefulness. Here, we review the mechanisms that lead to an increase in TKV in ADPKD, and examine the evidence supporting the conclusion that TKV provides a metric of disease progression that can be used to assess the efficacy of potential therapeutic regimens in children and adults with ADPKD. Moreover, we propose that TKV can be used to monitor treatment efficacy in patients with normal levels of renal function, before the pathologic processes of ADPKD cause extensive fibrosis and irreversible loss of functioning renal tissue.

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“…Based on our findings, vascular dysfunction in ADPKD is related to endothelial function (FMD) and potentially atherosclerosis (cIMT) more than to fluid overload (PWV) or cardiac failure (echocardiography). We [16, 17] and others [18, 19] have previously reported an impaired vascular function during early-stage ADPKD in cross-sectional studies and single modalities assessing vascular functions, while Peterson et al [20] studied endothelium-dependent vasodilation in a rat model of ADPKD and reported changes there that preceded a rise in mean arterial pressure or drop in GFR. With the present data, these findings are extended and broadened, demonstrating the consistent nature of ADPKD vasculopathy (early onset, FMD worse than cIMT, which in turn is worse than PWV and precedes any changes in cardiac geometry) as well as the extent to which vascular decline precedes that of GFR and also develops at a faster rate.…”

Section: Discussionmentioning

confidence: 99%

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease

et al. 2016

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BackgroundIn this study, we examined the relative usefulness of serum copeptin levels as a surrogate marker of vasopressin (AVP) in adult polycystic kidney disease (ADPKD) by correlating it with baseline and longitudinal changes in markers of both renal function and common CVD manifestations (hypertensive vascular disease, atherosclerosis and endothelial dysfunction) that accompany the progression of this disease.MethodsWe studied a cohort of young and otherwise healthy ADPKD patients (n = 235) and measured cardiovascular function using flow-mediation dilatation (FMD), carotid intima media thickness (cIMT) and pulse wave velocity (PWV), as well as serum copeptin (commercial ELISA, a stable marker of AVP activity). The same analyses were carried out at baseline and after 3 years of follow-up.ResultsAt baseline, median eGFR was 69 mL/min./1.73 m2, mean FMD 6.9 ± 0.9%, cIMT 0.7 ± 0.1 mm, and PWV 8.1 ± 1.2 m/s. At follow-up, equivalent values were 65 (44–75) mL/min./1.73 m2, 5.8 ± 0.9%, 0.8 ± 0.1 mm. and 8.2 ± 1.3 m/s. with all changes statistically significant. Plasma copeptin also rose from 0.62 ± 0.12 to 0.94 ± 0.19 ng/mL and this change correlated with ΔeGFR (-0.33, p < 0.001), ΔFMD (0.599, p < 0.001), ΔcIMT (0.562, p < 0.001) and ΔPWV (0.27, p < 0.001) also after linear regression modeling to correct for confounders. Finally, ROC analysis was done for a high baseline copeptin with ΔeGFR [cut-off:≤59], ΔFMD [cut-off: ≤7.08], ΔcIMT [cut-off:>0.76], and ΔPWV [cut-off:≤7.80].ConclusionsVascular dysfunction as reflected by FMD and cIMT, but not PWV or an altered cardiac geometry, precede most other signs of disease in ADPKD but is predicted by elevated levels of the circulating AVP-marker copeptin.

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Early renal and vascular changes in ADPKD patients with low-grade albumin excretion and normal renal function

Cited by 25 publications

References 26 publications

Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms

Similar renal outcomes in children with ADPKD diagnosed by screening or presenting with symptoms

The importance of total kidney volume in evaluating progression of polycystic kidney disease

Vasopressin-related copeptin is a novel predictor of early endothelial dysfunction in patients with adult polycystic kidney disease

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