Urinary renin-angiotensin markers in polycystic kidney disease

Salih, Mahdi; Bovée, Dominique M; Roksnoer, Lodi C.W.; Casteleijn, Niek F.; Bakker, Stephan J. L.; Gansevoort, Ronald; Zietse, Robert; Danser, A.H. Jan; Hoorn, Ewout J.

doi:10.1152/ajprenal.00209.2017

Cited by 21 publications

(18 citation statements)

References 42 publications

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“…Kocyigit et al also found that the urinary AGT/Cr ratio was significantly associated with SBP [26], and reported that it was higher in hypertensive patients with PKD than healthy controls. A recent study by Salih et al compared circulating and urinary RAAS components between patients with PKD and those with CKD but without PKD [27]; after adjusting for sex, eGFR, blood pressure, and RAAS inhibitor use between groups, the urinary AGT level and renin excretion were 5- to 6-fold higher in PKD than non-PKD patients, whereas circulating levels were not different. This was consistent with the findings in our study.…”

Section: Discussionmentioning

confidence: 99%

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

et al. 2019

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Background: Guidelines for general hypertension treatment do not recommend the combined use of reninangiotensin-aldosterone system (RAAS) inhibitors due to the risk of hyperkalemia. However, a recent clinical trial showed that polycystic kidney disease (PKD) patients had infrequent episodes of hyperkalemia despite receiving combined RAAS inhibitors. Because intrarenal RAAS is a main component for renal potassium handling, we further investigated the association between intrarenal RAAS activity and serum potassium level in patients with chronic kidney disease, particularly in PKD patients, and examined whether intrarenal RAAS activity has a prognostic role in patients with PKD. Methods: A total of 1788 subjects from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) were enrolled in this study. Intrarenal RAAS activity was assessed by the measurement of urinary angiotensinogen (AGT). The primary outcome was the composite of all-cause mortality and renal function decline. Results: Patients with PKD had a significantly lower serum potassium level in chronic kidney disease stages 1 to 3b than non-PKD patients. In logistic regression analysis, after adjusting for multiple confounders, PKD patients had a significantly lower risk of hyperkalemia than non-PKD patients. In multivariable linear regression analysis, the urinary AGT/creatinine (Cr) ratio was negatively correlated with the serum potassium level (β = − 0.058, P = 0.017) and positively correlated with the transtubular potassium gradient (TTKG, β = 0.087, P = 0.001). In propensity score matching analysis, after matching factors associated with serum potassium and TTKG, PKD patients had a significantly higher TTKG (P = 0.021) despite a lower serum potassium level (P = 0.004). Additionally, the urinary AGT/Cr ratio was significantly higher in PKD patients than in non-PKD patients (P = 0.011). In 293 patients with PKD, high urinary AGT/Cr ratio was associated with increased risk of the composite outcome (hazard ratio 1.29; 95% confidence interval, 1.07-1.55; P = 0.007). Conclusions: High activity of intrarenal RAAS is associated with increased urinary potassium excretion and low serum potassium level in patients with PKD. In addition, intrarenal RAAS activity can be a prognostic marker for mortality and renal function decline in these patients.

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Section: Discussionmentioning

confidence: 99%

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

et al. 2019

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“…Yet, there is a gap, and limited research focus was on the risk predictors for kidney disease. Some of the proposed candidates are neutrophil gelatinase-associated lipocalin, angiotensinogen, renin, and NEP (20,29,33,42,49,56). In addition, other RAS enzymes, such as urinary ACE and ACE2, have also been investigated as potential new markers for hypertension (6) and diabetes (28).…”

Section: Discussionmentioning

confidence: 99%

Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes

Gutta

Grobe

Kumbaji

et al. 2018

American Journal of Physiology-Renal Physiology

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Angiotensin converting enzyme 2 (ACE2) and neprilysin (NEP) are metalloproteases that are highly expressed in the renal proximal tubules. ACE2 and NEP generate renoprotective angiotensin (1-7) from angiotensin II and angiotensin I, respectively, and therefore could have a major role in chronic kidney disease (CKD). Recent data demonstrated increased urinary ACE2 in patients with diabetes with CKD and kidney transplants. We tested the hypothesis that urinary ACE2, NEP, and a disintegrin and metalloproteinase 17 (ADAM17) are increased and could be risk predictors of CKD in patients with diabetes. ACE2, NEP, and ADAM17 were investigated in 20 nondiabetics (ND) and 40 patients with diabetes with normoalbuminuria (Dnormo), microalbuminuria (Dmicro), and macroalbuminuria (Dmacro) using ELISA, Western blot, and fluorogenic and mass spectrometric-based enzyme assays. Logistic regression model was applied to predict the risk prediction. Receiver operating characteristic curves were drawn, and prediction accuracies were calculated to explore the effectiveness of ACE2 and NEP in predicting diabetes and CKD. Results demonstrated that there is no evidence of urinary ACE2 and ADAM17 in ND subjects, but both enzymes were increased in patients with diabetes, including Dnormo. Although there was no detectable plasma ACE2 activity, there was evidence of urinary and plasma NEP in all the subjects, and urinary NEP was significantly increased in Dmicro patients. NEP and ACE2 showed significant correlations with metabolic and renal characteristics. In summary, urinary ACE2, NEP, and ADAM17 are increased in patients with diabetes and could be used as early biomarkers to predict the incidence or progression of CKD at early stages among individuals with type 2 diabetes.

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“…More recent work has demonstrated that angiotensin II can be synthesised by, and act on, various tissues independent of the circulating RAS [18]. In ADPKD patients and animal models, the circulating RAS is not consistently elevated, as assessed through measurements of plasma renin concentration or enzymatic activity [5,19]. In contrast, urinary angiotensinogen and renin, thought to reflect the activity of the intrarenal RAS, are elevated in these patients [19].…”

Section: Hypertension In Pkdmentioning

confidence: 99%

“…In ADPKD patients and animal models, the circulating RAS is not consistently elevated, as assessed through measurements of plasma renin concentration or enzymatic activity [5,19]. In contrast, urinary angiotensinogen and renin, thought to reflect the activity of the intrarenal RAS, are elevated in these patients [19]. Upregulation of the intra-renal RAS could contribute to the development of hypertension in PKD, though causation has not been demonstrated.…”

Section: Hypertension In Pkdmentioning

confidence: 99%

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

Underwood¹,

Phillips²,

Hildreth³

2018

Ann Nutr Metab

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Polycystic kidney disease (PKD) is a group of monogenetic conditions characterised by the progressive accumulation of multiple renal cysts and hypertension. One of the earliest features of PKD is a reduction in urinary concentrating capacity that impairs extracellular fluid conservation. Urinary concentrating impairment predisposes PKD patients to periods of hypohydration when fluid loss is not adequately compensated by fluid intake. The hypohydrated state provides a blood hyperosmotic stimulus for vasopressin release to minimise further water loss. However, over-activation of renal V₂ receptors contributes to cyst expansion. Although suppressing vasopressin release with high water intake has been shown to impair disease progression in rodent models, whether this approach is efficacious in patients remains uncertain. The neural osmoregulatory pathway that controls vasopressin secretion also exerts a stimulatory action on vasomotor sympathetic activity and blood pressure during dehydration. Recurrent dehydration leads to a worsening of hypertension in rodents and cross-sectional data suggests that reduced urinary concentrating ability may contribute to hypertension development in the clinical PKD population. Experimental studies are required to evaluate this hypothesis and to determine the underlying mechanism.

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Urinary renin-angiotensin markers in polycystic kidney disease

Cited by 21 publications

References 42 publications

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

Urinary angiotensinogen level is associated with potassium homeostasis and clinical outcome in patients with polycystic kidney disease: a prospective cohort study

Increased urinary angiotensin converting enzyme 2 and neprilysin in patients with type 2 diabetes

Osmoregulation in Polycystic Kidney Disease: Relationship with Cystogenesis and Hypertension

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