D-Serine mediates cellular proliferation for kidney remodeling

Background: D-Serine, a long-term undetected enantiomer of serine, is a biomarker that reflects kidney function and disease activity. The physiological functions of D-serine have been unclear. Methods: Dynamics of D-serine was assessed by measuring D-serine in human samples of living kidney donors using two-dimensional high-performance liquid chromatography, and by auto-radiographic studies in mice. Effects of D-serine on kidney were examined by gene expression profiling and metabolic studies using unilateral nephrectomy mice, and genetically modified cells. Results: Unilateral nephrectomy in human living kidney donors decreases urinary excretion and thus increases the blood level of D-serine. D-Serine is quickly and dominantly distributed to the kidney upon injection in mice, suggesting that the kidney is a main target organ. Treatment of D-serine at low dose promotes the enlargement of remnant kidney in mouse model. Mechanistically, D-serine activates the cell cycle for tissue remodeling through an mTOR-related pathway. Conclusions: D-Serine is a physiological molecule that promotes kidney remodeling. Besides its function as a biomarker, D-serine has a physiological activity that influences kidney function.

Huoxue Jiedu Huayu Formula Alleviates Cell Pyroptosis in Contralateral Kidneys of 6-Month-Old UUO Rats through the NLRP3/Caspase-1/IL-1β Pathway

Objectives. To study the protective effects and mechanisms of Huoxue Jiedu Huayu formula on cell pyroptosis through the NLRP3/caspase-1/IL-1β pathway in contralateral kidneys in 6-month-old unilateral ureteral obstruction (UUO) rats. Methods. Wistar rats were randomly assigned to 5 groups: a Sham group, a unilateral nephrectomy group (UNX group), a UUO group, a UUO treated with spironolactone group (Spi group), and a UUO treated with Huoxue Jiedu Huayu formula group (HJHF group). After 6 months of oral drug intervention, blood and contralateral kidneys were collected for research. Results. The morphology and function of the contralateral kidneys were essentially normal after unilateral nephrectomy. HJHF obviously decreased serum creatinine, urea, and inflammatory lesions and depressed cell pyroptosis based on the NLRP3/caspase-1/IL-1β pathway. Moreover, spironolactone, a mineralocorticoid receptor (MR) blocker, suppressed cell pyroptosis through SGK-1 and NF-кB. Conclusion. HJHF and spirolactone inhibited excessive activation of MR and then reduced cell pyroptosis, which was dependent on the NLRP3/caspase-1/IL-1β pathway, to protect the contralateral kidneys of 6-month-old UUO rats.

The release of hydrolytic enzymes by the salivary glands and their content in the blood after unilateral nephrectomy

We studied the mechanisms of transformation of some salivary enzymes and established the real contribution of the salivary glands to the enzymatic homeostasis of the body in unilateral nephrectomy.The results were obtained that with unilateral nephrectomy, the content of amylase and pepsinogen in the blood increases, but its lipolytic activity remains unchanged, the volume of basal secretion of the salivary glands, the content and release of amylase by the parotid salivary gland increases. Unilateral nephrectomy stimulates the increment of pepsinogen by the gastric glands, and, accordingly, enhances its recreation from the blood, by the salivary glands. After unilateral nephrectomy, lipolytic activity and its secretion in saliva remain unchanged

Urine NGAL and KIM-1—Tubular Injury Biomarkers in Long-Term Survivors of Childhood Solid Tumors: A Cross-Sectional Study

The deterioration of renal function after childhood solid tumors treatment is the result of using the intensive multimodal therapy. In recent years, urinary kidney injury molecule-1 (KIM-1) and urinary neutrophil gelatinase-associated lipocalin (NGAL) have been introduced as potential promising biomarkers of early kidney damage. The aim of the present study was to determine whether anticancer treatment has any effect on the concentration of KIM-1 and NGAL and its association with renal impairment in survivors of childhood solid tumors. Sixty patients previously treated for solid tumors were involved in this study. The median time after end of treatment was 8.35 years. Urine KIM-1 and NGAL levels were measured using immunoenzymatic ELISA commercial kits. Higher levels of urine NGAL, KIM-1/cr. (creatinine), and NGAL/cr. ratios were found in comparison with healthy controls (p < 0.0001). Among all subjects, 23% were found to have decreased estimated glomerular filtration rate (eGFR). A strong correlation between KIM-1/cr. and a cumulative dose of ifosfamide was observed (r = 0.865, p < 0.05). In addition, a moderate correlation between NGAL/cr. and a cumulative dose of cisplatin was identified (r = 0.534, p < 0.05). The AUC for KIM-1/cr. was 0.52, whereas NGAL/cr. showed a diagnostic profile describing the AUC of 0.67. Univariable regression showed significant associations between NGAL/cr. ratio and subjects after unilateral nephrectomy (coeff. 63.8, p = 0.007), cumulative dose of cisplatin (coeff. 0.111, p = 0.033), and age at diagnosis (coeff. 3.75, p = 0.023). The multivariable model demonstrated only cumulative dose of cisplatin as an independent factor influence on NGAL/cr. ratio. The results of our study showed increased levels of urine KIM-1 and NGAL many years after completion of the childhood solid tumors treatment, which correlated positively with a cumulative dose of ifosfamide and cisplatin. This study also suggests that unilateral nephrectomy could affect the concentration of the studied biomarkers.

Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study

Background We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. Methods We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. Results In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039–1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693–11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104–6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884–18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92–26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. Conclusions Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.

A case of renovascular hypertension with incidental primary bilateral macronodular adrenocortical hyperplasia

Summary Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and low-level autonomous cortisol secretion. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of a disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg, pulse rate was 132 beats/min, and plasma glucose level was 712 mg/dL. Abdominal CT scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. His left adrenal lobular mass was over 40 mm and it was clinically suspected the potential for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed, resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, the activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy. Learning points: Concomitant activation of the renin-angiotensin-aldosterone system and cortisol overproduction may contribute to the development of severe hypertension and lead to lethal cardiovascular complications. Treatment with simultaneous unilateral nephrectomy and adrenalectomy markedly improves BP and blood glucose levels. CYP11B2 immunohistochemistry staining revealed the existence of aldosterone-producing cell clusters (APCCs) in the adjacent non-nodular adrenal gland, suggesting that APCCs may contribute to aldosterone overproduction in patients with RVHT.