Compensatory renal hypertrophy following uninephrectomy is calcineurin‐independent

Williams, Clintoria R.; Wynne, Brandi M.; Walker, Makeeva; Hoover, Robert S.; Gooch, Jennifer

doi:10.1111/jcmm.12438

Cited by 7 publications

(4 citation statements)

References 31 publications

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“…Harris has shown that the observed increase in blood flow through the remnant kidney and the consecutively increased amino acid delivery activates a class III phosphatidylinositol‐3 kinase that induces mechanistic target of rapamycin complex 1 (mTORC1)/p70 ribosomal protein kinase 1 (S6K1) signaling and thereby the compensatory increase in kidney size. However, the compensatory growth of the remnant kidney amounts to ≈20% such that not only the filtration and transport capacities, but also the metabolic functions are presumably not fully compensated.…”

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confidence: 99%

Kidney Mass Reduction Leads to l ‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice

Pillai

Seebeck

Fingerhut

et al. 2018

JAHA

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BackgroundUninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l‐arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l‐arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice.Methods and ResultsIn a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post‐UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l‐citrulline, that is used in the kidney to produce l‐arginine, was elevated post‐UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l‐arginine and is a marker for renal failure. Interestingly, the UNX‐induced blood pressure increase was prevented by supplementation of the diet with 5% of the l‐arginine precursor, l‐citrulline. Because l‐arginine is metabolized in the kidney and other peripheral tissues by arginase‐2, we tested whether the lack of this metabolic pathway also compensates for decreased l‐arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase‐2 knockout mice (Arg‐2−/−) neither displayed an increase in asymmetric dimethylarginine and l‐citrulline plasma levels nor a significant increase in blood pressure.ConclusionsUNX leads to a small increase in blood pressure that is prevented by l‐citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l‐arginine metabolism.

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confidence: 99%

Kidney Mass Reduction Leads to l ‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice

Pillai

Seebeck

Fingerhut

et al. 2018

JAHA

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“…Conversely, in a model of diabetic-nephropathy, uninephrectomy enhanced the formation of pathophysiologic changes [ 21 ]. As for salt overload, the adaptative processes following uninephrectomy include proximal-tubular hypertrophy [ 22 ]. A beneficial role of sodium-glucose-cotransporter-2 (SGLT-2) inhibition was shown in uninephrectomized KK/Ay type 2 diabetic mice providing indirect evidence for upregulated SGLT-2, when kidney mass is reduced [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Experimental uninephrectomy associates with less parasympathetic modulation of heart rate and facilitates sodium-dependent arterial hypertension

Pliquett

Brandes

2022

PLoS ONE

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Background Blood pressure is known to be increased in kidney donors following living-donor kidney transplantation. However, the physiological underpinnings of the blood-pressure increase following uninephrectomy remain unclear. We hypothesized that changes in sympathetic tone or in parasympathetic modulation of sinus node function are involved in the blood-pressure increase following experimental kidney-mass reduction. Methods C57BL6N mice (6 to 11 per group) subjected to sham surgery (controls) or uninephrectomy with or without a one-week course of sodium chloride-enriched, taurine-deficient diet were studied. Uninephrectomized mice treated with a subcutaneous infusion of angiotensin-II over a period of one week were positive controls. A transfemoral aortic catheter with telemetry unit was implanted, readings of heart-rate and blood-pressure were recorded. Powerspectral analysis of heart rate and systolic blood pressure was performed to gain surrogate parameters of sympathetictone and parasympathetic modulation of sinus node function. Baroreflex sensitivity of heart rate was determined from awake, unrestrained mice using spontaneous baroreflex gain technique. Results Systolic arterial blood pressure, heart rate and baroreflex sensitivity were not different in uninephrectomized mice when compared to controls. Parasympathetic modulation of sinus node function was less in uninephrectomized mice in comparison to controls. Uninephrectomized mice of the high-angiotensin-II model or of the high-salt and taurine-deficiency model had an increased systolic arterial blood pressure. Conclusions Uninephrectomy associated with less parasympathetic modulation of sinus node function. The combination of uninephrectomy, taurine-deficiency and high-salt intake led to arterial hypertension.

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“…According to research [28,29], renal compensatory hypertrophy restores normal renal function after nephrectomy due to an increase in organ size due to cell growth, and not their proliferation [17].…”

Section: Discussionmentioning

confidence: 99%

Organometric parameters of the remaining kidney after removal of the contralateral in immature rats

Моnastyrskyi

2018

Rep. of Morph.

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The processes of compensatory hypertrophy of the kidney to the period of puberty are insufficiently studied. Changes in renal parameters after contralateral removal are of scientific interest. The purpose of the study was to establish and compare changes in organometric parameters of the kidney that remained after nephrectomy in non-sexually adult male rats and in sexually mature male rats. Experimental study was performed on 84 non-adult white male rats weighing 53-71 grams, which were kept on a standard vivarium diet. All animals were divided into two groups (42 in each): the first - control, the second - the experimental group. In the control group, the abdominal cavity was opened under ketamine anesthesia, after wich the abdominal wall was sutured in layers. All animals of the experimental group performed surgical intervention - nephrectomy of the left kidney. Animals were withdrawn from the trial by intra-pleural administration of thiopental-sodium 50 mg/kg after 7, 14, 21, 30, 90 days after nephrectomy. Macroscopic evaluation and description of the kidneys of animals was performed after their removal. The statistical analysis of the obtained results was carried out using the “STATISTICA 5.5” program, using parametric and non-parametric methods for evaluating the obtained results. It was found that in the immature rats, the weight of animals in the experimental group (after nephrectomy) was statistically significantly lower in all terms of the observation compared to the control group, and the weight of the kidney of animals in the experimental group, on the contrary, was statistically significantly higher in all terms of observation. The length, width, thickness, volume of kidneys of animals of the experimental group, as well as the magnitude of increment of these parameters with each term of observation are determined. The greatest increase in organometric parameters of the kidney was observed after 30 days of the postoperative period (p<0.05). Subsequently, on the 60th and 90th day, the magnitude of the increase in organometric parameters of the kidney significantly decreased. The index of hypertrophy of the kidney remained unpaired by nephrectomy, which varied from 52.24% to 63.21%. The highest rates of hypertrophy were observed between the 21st and 30th days.

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Compensatory renal hypertrophy following uninephrectomy is calcineurin‐independent

Cited by 7 publications

References 31 publications

Kidney Mass Reduction Leads to l ‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice

Kidney Mass Reduction Leads to l ‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice

Experimental uninephrectomy associates with less parasympathetic modulation of heart rate and facilitates sodium-dependent arterial hypertension

Organometric parameters of the remaining kidney after removal of the contralateral in immature rats

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