High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease

Kapoor, Sarika; Rodríguez, Daniel; Mitchell, Katharyn J; Wüthrich, Rudolf P.

doi:10.1159/000443420

Cited by 5 publications

(4 citation statements)

References 22 publications

(26 reference statements)

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“…There are currently no prognostic tools to identify ADPKD patients with high cardiovascular risk [65]. The early and noninvasive evaluation of inflammatory indexes, endothelial dysfunction, atherosclerotic markers and HOMA-IR, in addiction to mineral metabolism indexes and cTnT may be necessary to improve the cardiovascular prognosis of affected patients, especially in the early stages of disease, when renal function is still preserved, despite the cost implication.…”

Section: Resultsmentioning

confidence: 99%

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai

Mastroluca

Matino

et al. 2017

Kidney Blood Press Res

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Background/Aims: Cardiovascular disease is the most frequent cause of morbidity and mortality in autosomal dominant polycystic kidney disease (ADPKD) patients, often before the onset of renal failure, and the pathogenetic mechanism is not yet well elucidated. The aim of the study was to identify early and noninvasive markers of cardiovascular risk in young ADPKD patients, in the early stages of disease. Methods: A total of 26 patients with ADPKD and 24 control group, matched for age and sex, were enrolled, and we have assessed inflammatory indexes, mineral metabolism, metabolic state and markers of atherosclerosis and endothelial dysfunction (carotid intima media thickness (IMT), ankle brachial index (ABI), flow mediated dilation (FMD), renal resistive index (RRI), left ventricular mass index (LVMI)) and cardiopulmonary exercise testing (CPET), maximal O₂ uptake (V’O₂max), and O₂ uptake at lactic acid threshold (V’O₂@LT). Results: The ADPKD patients compared to control group, showed a significant higher mean value of LVMI, RRI, homocysteine (Hcy), Homeostasis Model Assessment-insulin resistance (HOMA-IR), serum uric acid (SUA), Cardiac-troponinT (cTnT) and intact parathyroid hormone (iPTH) (p<0.001, p<0.001, p<0.001, p<0.001, p<0.001, p=0.007, p=0.019; respectively), and a lower value of FMD and 25-hydroxyvitaminD (25-OH-VitD) (p<0.001, p<0.001) with reduced parameters of exercise tolerance, as V’O₂max, V’O₂max/Kg and V’O₂max (% predicted) (p<0.001, p<0.001, p=0.018; respectively), and metabolic response indexes (V’O₂@LT, V’O₂ @LT%, V’O₂@LT/Kg,) (p<0.001, p=0.14, p<0.001; respectively). Moreover, inflammatory indexes were significantly higher in ADPKD patients, and we found a positive correlation between HOMA-IR and C-reactive protein (CRP) (r=0.507, p=0.008), and a negative correlation between HOMA-IR and 25-OH-VitD (r=-0.585, p=0.002). Conclusion: In our study, ADPKD patients, in the early stages of disease, showed a greater insulin resistance, endothelial dysfunction, inflammation and mineral metabolism disorders, respect to control group. Moreover, these patients presented reduced tolerance to stress, and decreased anaerobic threshold to CPET. Our results indicate a major and early cardiovascular risk in ADPKD patients. Therefore early and noninvasive markers of cardiovascular risk and CPET should be carried out, in ADPKD patients, in the early stages of disease, despite the cost implication.

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Section: Resultsmentioning

confidence: 99%

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Lai

Mastroluca

Matino

et al. 2017

Kidney Blood Press Res

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“…First, the degree of cyst growth differs between PCK rats and humans with PKDs. Although the cysts in human patients spread from the surface of the kidney and compress the surrounding organs, most cysts formed in the PCK rats remained within the enlarged kidneys [20,30,31]. Second, the degree of renal dysfunction in the PCK rats was relatively slight, compared to the degree of tubulointerstitial damage.…”

Section: Discussionmentioning

confidence: 96%

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

Watanabe

Ichikawa

Sugaya

et al. 2018

Kidney Blood Press Res

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Background/Aims: Polycystic kidney disease (PKD) is a common, progressive, and heritable type of kidney disease. Although certain imaging modalities are useful for the diagnosis and staging of PKD, they cannot adequately monitor the severity of interstitial inflammation and fibrosis. Therefore, the present study evaluated the urinary level of liver-type fatty acid binding protein (L-FABP) as a marker of interstitial inflammation and fibrosis in PKD. Methods: Male PCK/CrljCrl-Pkhd1pck/Crl (PCK) rats (n = 34) were used as an animal model of the PKD. Age-and sex-matched Sprague–Dawley rats (SD) (n = 34) were used as controls. Urine samples were obtained from the rats at 8, 12, 16, 20, and 24 weeks of age, and the sera and kidney tissues were obtained at 8, 16, 20, and 24 weeks of age. Results: All PCK rats developed cysts, and the degrees of tubular epithelial cell proliferation and interstitial inflammation increased linearly with age in these model rats relative to the controls. Interstitial fibrosis tended to increase in the PCK rats from 8 to 20 weeks of age, and revealed a peak level at 20 weeks. The urinary L-FABP levels increased linearly with age in the PCK rats, and the levels at 12, 16, 20, and 24 weeks were significantly higher than those in the controls. The urinary levels of L-FABP in the PCK rats correlated significantly with the severity of tubulointerstitial damage; specifically, we observed a significant correlation of the urinary levels at 16 weeks of age with the total kidney volume at 20 weeks. In contrast, both PCK and SD rats exhibited similar serum levels of L-FABP. Conclusion: Urinary L-FABP reflects the progression of tubulointerstitial damage, and therefore, may be a useful marker for monitoring the progression of PKD.

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“…Therefore, there is a great need for a reliable technique that can accurately assess LV in this animal model and further that allows repeated measurements during drug treatment. High Resolution Ultrasonography has recently been used to assess renal cysts in the PCK rats[ 22 ]. Also, as an indirect assessment method, T1 relaxation time was proposed as an imaging marker of liver disease for the PCK model[ 23 ] but neither of these was used to determined LV.…”

Section: Discussionmentioning

confidence: 99%

Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

Temmerman¹,

Chen²,

Libbrecht³

et al. 2017

WJG

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AIMTo develop a MRI-based method for accurate determination of liver volume (LV) and to explore the effect of long-term everolimus (EVR) treatment on LV in PCK rats with hepatomegaly.METHODSThirty-one female PCK rats (model for polycystic-liver-disease: PCLD) were randomized into 3 groups and treatment was started at 16 wk, at the moment of extensive hepatomegaly (comparable to what is done in the human disease). Animals received: controls (n = 14), lanreotide (LAN: 3 mg/kg per 2 wk) (n = 10) or everolimus (EVR: 1 mg/kg per day) (n = 7). LV was measured at week 16, 24, 28. At week 28, all rats were sacrificed and liver tissue was harvested. Fibrosis was evaluated using quantitative image analysis. In addition, gene (quantitative RT-PCR) and protein expression (by Western blot) of the PI3K/AkT/mTOR signaling pathway was investigated.RESULTSLV determination by MRI correlated excellent with the ex vivo measurements (r = 0.99, P < 0.001). The relative changes in LV at the end of treatment were: (controls) +31.8%; (LAN) +5.1% and (EVR) +8.8%, indicating a significantly halt of LV progression compared with controls (respectively, P = 0.01 and P = 0.04). Furthermore, EVR significantly reduced the amount of liver fibrosis (P = 0.004) thus might also prevent the development of portal hypertension. There was no difference in phosphorylation of Akt (Threonine 308) between LAN-treated PCK rats control PCK rats, whereas S6 was significantly more phosphorylated in the LAN group. Phosphorylation of Akt was not different between controls and EVR treated rats, however, for S6 there was significantly less phosphorylation in the EVR treated rats. Thus, both drugs interact with the PI3K/AkT/mTOR signaling cascade but acting at different molecular levels.CONCLUSIONEverolimus halts cyst growth comparable to lanreotide and reduces the development of fibrosis. mTOR-inhibition should be further explored in PCLD patients especially those that need immunosuppression.

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High Resolution Ultrasonography for Assessment of Renal Cysts in the PCK Rat Model of Autosomal Recessive Polycystic Kidney Disease

Cited by 5 publications

References 22 publications

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Early Markers of Cardiovascular Risk in Autosomal Dominant Polycystic Kidney Disease

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

Everolimus halts hepatic cystogenesis in a rodent model of polycystic-liver-disease

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