Renal tissue oxygenation in children with chronic kidney disease due to vesicoureteral reflux

CAKUT-syndrome includes combined congenital abnormalities of the kidneys and urinary tract and is a complex problem in pediatrics, requiring an interdisciplinary approach of doctors of various specialties. One of the most severe manifestations of CAKUT-syndrome is vesicoureteral reflux, which is often the main manifestation of a congenital abnormality of the kidneys and urinary tract. Structural and urodynamic disorders in the organs of the urinary system in vesicoureteral reflux can lead to the formation of reflux nephropathy and chronic kidney disease. Low-symptom clinical manifestations of reflux nephropathy make it difficult to diagnose it early. Vesicoureteral reflux leads to intrarenal reflux, repeated attacks of pyelonephritis and sclerosis of the renal tissue, which in 25-60 % of cases causes end-stage chronic renal failure due to vesicoureteral reflux. Given the absence of specific pathognomonic clinical manifestations of reflux nephropathy, laboratory indicators are of fundamental importance in the diagnosis-levels of albuminuria, leukocyturia, urinary sediment fermenturia, urine osmolarity, daily urinary excretion of β2 – microglobulin and a wide arsenal of methods for diagnosing reflux nephropathy and scarring of the renal parenchyma: ultrasound with dopplerography of the renal blood flow, magnetic resonance imaging and computed tomography, radioisotope scanning. The imperfection of instrumental methods for visualizing the initial stages of kidney fibrosis dictates the need to develop alternative, more sensitive methods for early diagnosis of reflux nephropathy. One of the directions of this search is molecular diagnostics, which allows you to detect possible damage to the renal tissue at the subcellular level long before the clinical manifestations of pathology, personify nephroprotective therapy and prevention of reflux nephropathy. The article presents clinical observations from our own practice of late diagnosis of reflux nephropathy, in which renal pathology was first detected at stages 5 and 3 of chronic kidney disease in two boys aged 10 and 16 years, respectively, who were on inpatient treatment in the Nephrology Department of the Children's Republican clinical hospital.

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Altered Emotional Phenotypes in Chronic Kidney Disease Following 5/6 Nephrectomy

Brain Sciences ◽

10.3390/brainsci11070882 ◽

2021 ◽

Vol 11 (7) ◽

pp. 882

Author(s):

Yeon Hee Yu ◽

Seong-Wook Kim ◽

Dae-Kyoon Park ◽

Ho-Yeon Song ◽

Duk-Soo Kim ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Local Field ◽

Smooth Muscle Actin ◽

Local Field Potentials ◽

Renal Tissue ◽

Field Potentials ◽

Wild Type ◽

Sprague Dawley ◽

Rat Models

Increased prevalence of chronic kidney disease (CKD) and neurological disorders including cerebrovascular disease, cognitive impairment, peripheral neuropathy, and dysfunction of central nervous system have been reported during the natural history of CKD. Psychological distress and depression are serious concerns in patients with CKD. However, the relevance of CKD due to decline in renal function and the pathophysiology of emotional deterioration is not clear. Male Sprague Dawley rats were divided into three groups: sham control, 5/6 nephrectomy at 4 weeks, and 5/6 nephrectomy at 10 weeks. Behavior tests, local field potentials, and histology and laboratory tests were conducted and investigated. We provided direct evidence showing that CKD rat models exhibited anxiogenic behaviors and depression-like phenotypes, along with altered hippocampal neural oscillations at 1–12 Hz. We generated CKD rat models by performing 5/6 nephrectomy, and identified higher level of serum creatinine and blood urea nitrogen (BUN) in CKD rats than in wild-type, depending on time. In addition, the level of α-smooth muscle actin (α-SMA) and collagen I for renal tissue was markedly elevated, with worsening fibrosis due to renal failures. The level of anxiety and depression-like behaviors increased in the 10-week CKD rat models compared with the 4-week rat models. In the recording of local field potentials, the power of delta (1–4 Hz), theta (4–7 Hz), and alpha rhythm (7–12 Hz) was significantly increased in the hippocampus of CKD rats compared with wild-type rats. Together, our findings indicated that anxiogenic behaviors and depression can be induced by CKD, and these abnormal symptoms can be worsened as the onset of CKD was prolonged. In conclusion, our results show that the hippocampus is vulnerable to uremia.

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Pharmacokinetics and Pharmacodynamics of the Combination of Rhein and Curcumin in the Treatment of Chronic Kidney Disease in Rats

Frontiers in Pharmacology ◽

10.3389/fphar.2020.573118 ◽

2020 ◽

Vol 11 ◽

Author(s):

Xiaoying He ◽

Guowei Li ◽

Yuanyuan Chen ◽

Qiming Xiao ◽

Xinwei Yu ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Molecular Docking ◽

Kidney Disease ◽

Interaction Mechanism ◽

Ultra Performance Liquid Chromatography ◽

Renal Tissue ◽

Combination Group ◽

Sprague Dawley ◽

Pharmacokinetics And Pharmacodynamics ◽

Sd Rats

Objectives: The interaction between the components of traditional Chinese medicine (TCM) is an important basis for their synergy. Rhein and curcumin exert various pharmacological activities, including anti-tumour, anti-inflammatory, antioxidant, anti-fibrosis and renoprotective effects. However, no investigation has reported the synergistic anti-fibrosis effect yet. This study aims at determine the pharmacokinetics and pharmacodynamics of the combination of rhein and curcumin in the treatment for chronic kidney disease in rats.Design: Fifty two male Sprague-Dawley (SD) rats were randomly divided into rhein group, curcumin group and their combination group for pharmacodynamics studies. HE and Masson staining was conducted to observe the changes of renal morphology. Kits were used to detect the level of urea nitrogen (BUN) and creatinine (Scr). For pharmacokinetic study, 36 SD rats were randomly divided into rhein group, curcumin group and a combination group, the content of rhein and curcumin in plasma and renal tissue was determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). In additon, molecular docking method and cell experiments was used to disclose the interaction mechanism between curcumin and rhein.Results: The pharmacodynamic results showed that the degree of renal fibrosis was improved obviously by co-administration rhein and curcumin. Meanwhile, compared to single administration, the Cmax and AUC of rhein and curcumin in plasma and renal tissue were enhanced significantly after co-administration. Moreover, the result of molecular docking and cell experiments showed that both two compounds could interact with P-gp, CYP2C9 and CYP2C19.Conclusion: Together, these findings demonstrated that rhein and curcumin had a synergistic effect in ameliorateing chonic kidney disease, providing an important explanation on the synergistic mechanism of curcumin and rhein from a pharmacokinetic viewpoint.

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