Splenectomy attenuates the course of kidney ischemia-reperfusion injury in rats.

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) initiates inflammatory response with synthesis of free oxygen radicals, chemokines, and cytokines which attract neutrophils and monocytes, which then differentiate into macrophages and dendritic cells, activating adaptive immune response. The spleen is the main source of both monocytes and lymphocytes. The aim of this study was to assess whether splenectomy performed before or upon IRI affects post-ischemic and long-term renal function. METHODS: Two weeks after right nephrectomy, the left kidney pedicle was clamped for 45 minutes in 24 rats. After the clip insertion, the spleen was removed in 12 animals and the remaining 12 rats underwent sham splenectomy. In the second experiment, splenectomy (n = 9) or sham procedure (n = 9) was performed simultaneously with right nephrectomy, 2 weeks before left kidney ischemia. The excretory function of the kidney was evaluated 48 hours and 7 days after ischemia. In the experimental model of chronic renal failure, 14 days before right nephrectomy, the prolonged 90-minute ischemia was induced in 32 rats with simultaneous splenectomy (n = 16) or sham procedure (n = 16). In long-term observation, the renal function and mortality rate was evaluated. RESULTS: Kidney function preservation was superior in rats that underwent splenectomy together with renal ischemia when compared to controls. This was further expressed with a 2 times lower mortality rate in splenectomized animals in 6 months observation after prolonged renal ischemia. Renoprotective effect was not observed when splenectomy was performed 2 weeks before IRI. CONCLUSIONS: The results suggest a detrimental influence of the spleen on the development of renal IRI.

Nephroprotective effect of pentoxifylline in renal ischemia-reperfusion in rat depends on the timing of its administration.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) induces inflammatory reaction damaging kidney. Pentoxifylline (PTX) given before IRI attenuates inflammation and prevents ischemic acute kidney injury (iAKI). Given that in clinical settings IRI is not always predictable, we aimed to assess whether PTX administration during or shortly after IRI affects the course of iAKI in the rat. METHODS: In 58 male 10-week-old Sprague-Dawley rats, 14 days after right nephrectomy, a 45-minute clamping of solitary renal pedicle was conducted. PTX 100 mg/kg body weight or 0.9% NaCl 1 mL were given subcutaneously either 60 minutes before renal ischemia, 1 minute into ischemia, or 60 minutes after clamp release. Creatinine clearance (ClCr; mL/min/kg body weight), fractional excretions of sodium (FENa [%]) and potassium (FEK [%]), and urine protein/ClCr ratio (Uprot/ClCr [mg/1 mL ClCr]) at 48 hours after IRI were compared between PTX-treated animals and respective controls (Mann-Whitney U test). RESULTS: Kidney function was improved in rats given PTX before IRI compared with controls: ClCr 2.10 ± 0.44 versus 1.03 ± 0.18; FENa 0.16 ± 0.12 versus 0.84 ± 0.55; FEK 40.3 ± 13.0 versus 75.5 ± 17.9, respectively (all P < .001). There was no difference in proteinuria: Uprot/ClCr 0.004 ± 0.002 versus 0.004 ± 0.002. Conversely, the analyzed parameters did not differ between animals administered PTX during IRI and controls: ClCr 0.42 ± 0.34 versus 0.73 ± 0.43; FENa 2.98 ± 2.71 versus 3.16 ± 3.05; FEK 280.1 ± 155.7 versus 206.2 ± 154.1; and Uprot/ClCr 0.031 ± 0.029 versus 0.029 ± 0.031, respectively, nor between rats given PTX after IRI and controls: ClCr 0.29 ± 0.38 versus 0.40 ± 0.47; FENa 4.25 ± 3.55 versus 3.80 ± 3.94; FEK 284.9 ± 117.5 versus 243.0 ± 150.6; and Uprot/ClCr 0.044 ± 0.018 versus 0.055 ± 0.061, respectively. CONCLUSIONS: PTX given only before, and not at the time of renal ischemia or after reperfusion, alleviates subsequent iAKI in the rat. This implicates usefulness of PTX in the clinical settings of expected renal ischemia, like kidney transplantation, and suggests potential benefits of PTX in peritransplant period foremost with donor pretreatment.

Pentoxifylline augments fasting-induced nephroprotection in acute ischemic kidney injury in rats.

BACKGROUND: Prolonged fasting exerts anti-inflammatory effects, and pentoxifylline (PTX) has similar immunomodulating properties. OBJECTIVE: To compare the influence of feeding status and PTX administration on the course of acute ischemic kidney injury. MATERIAL AND METHODS: Seven days after right-sided nephrectomy and 7 days before renal ischemia, 44 male Sprague-Dawley rats were placed in individual cages with unlimited access to water. Rats were divided into 4 groups; groups Ia and Ib were fed with no limitations, and groups IIa and IIb were fasted for 32 hours before renal ischemia. Ninety minutes before clamping of the left kidney vascular pedicle, rats in groups Ib and IIb and those in groups Ia and IIa, respectively, were given either PTX subcutaneously, 100 mg per kilogram of body weight in 1 mL of 0.9% sodium chloride, or 0.9% sodium chloride only. Biochemical parameters of renal function were estimated at 48 hours after the ischemic event. RESULTS: Both fasting and PTX administration diminished the degree of ischemia-induced impairment of renal function. The combined effects were additive. CONCLUSIONS: Fasting and treatment with PTX during the preischemic period exerts additive nephroprotective effects in the setting of acute ischemic kidney injury. This finding may be useful in future practices of preservation and kidney transplantation.

[Levels of 1,25-dihydroxyvitamin D3 concentration in renal venous blood serum of patients with renovascular hypertension caused by unilateral renal artery stenosis]. / Stezenie 1,25-dihydroksycholekalcyferolu w surowicy krwi zylnej nerek u chorynch na nadcisnienie naczyniowonerkowe spowodowane jednostronnym zwezeniem tetnicy nerkowej.

UNLABELLED: Functionally significant, unilateral renal artery stenosis is characterized by reduced renal perfusion and lateralization of both excretory and endocrine function. The present study aimed to assess the influence of unilateral renal artery stenosis on plasma 1,25-dihydroxyvitamin D3 level. In sixteen patients (10 males and 6 females) with unilateral renovascular hypertension blood samples for estimation of plasma renin activity (PRA) and 1,25-dihydroxyvitamin D3 concentration were withdrawn from the renal vein of the ischaemic and normal kidney, from the femoral artery and from the vena cava inferior distally to the orifices of renal veins. Significantly elevated PRA (20.1 +/- 4.52 ng/ml/h vs 6.0 +/- 1.76 ng/ml/h, p < 0.005) but significantly reduced level of 1,25-dihydroxyvitamin D3 (99.25 +/- 4.8 pmol/l vs 115.75 +/- 6.7 pmol/l, p < 0.05) were found in renal vein blood of the ischaemic kidney as compared with the respective values of the normal kidney. No significant correlation was found between PRA and 1.25-dihydroxyvitamin D3 irrespective of the site of blood withdrawal. CONCLUSION: Renal ischaemia seems to exert a suppressive effect on 1,25-dihydroxyvitamin D3 synthesis by the kidney.

[Life threatening hypercalcemia in a patient with chronic renal failure. Case report]. / Hiperkalcemia zagrazajaca zyciu u chorej z przewlekla niewydolnoscia nerek. Opis przypadku.

In the present paper a 67 years old female with chronic renal failure is reported, who developed at least three episodes of live-threatening hypercalcemia during long-term therapy with calcium carbonate. Results of biochemical and hormonal parameters and of dual x-ray photon absorptiometry (DEXA) were indicative for the presence of adynamic bone disease. Results obtained in this patient and published in the literature suggest, that presence of subnormal plasma concentrations of intact parathyroid hormone seems to be a valuable predictor of hypercalcemia in uremic patients treated with calcium carbonate.

Decreased renal haemodynamic response to inhibition of nitric oxide synthase in subtotally nephrectomized rats.

To assess the renal haemodynamic response to manipulations of the nitric oxide (NO) system, we examined subtotally nephrectomized (SNX) rats and control rats (CON) 28 days after their operation. Bolus infusions of the NO synthase inhibitor NG-nitro-L-arginine (L-NA) were given intravenously at doses of 2 mg/kg and 10 mg/kg. Blood pressure was measured intra-arterially, glomerular filtration rate was measured by inulin clearance and fractional changes in renal blood flow (RBF) were determined by a Doppler flow probe. Both doses of L-NA caused a similar and dose-dependent increase in mean blood pressure in both SNX and CON rats. In contrast, the decrease in RBF and the increase in the renovascular resistance index (RVRI) was less in SNX rats as compared to CON rats (RBF = -70.1 +/- 2.2% of baseline vs -52.7 +/- 5.2%, P < 0.01; RVRI = +177 +/- 9% of baseline vs +243 +/- 24%, P < 0.05). These changes were not affected by autonomic blockade (hexamethonium), or by blockade of the angiotensin II receptor (Losartan). The exogenous NO donor sodium nitroprusside (0.5 and 1.5 micrograms.kg-1.min-1) lowered mean blood pressure to a similar degree in SNX and CON rats; in contrast, RVRI decreased less in SNX rats (86.9 +/- 9.2% of baseline) than in CON rats (68.2 +/- 4.6%, P < 0.05). We conclude that the reaction of the renal vasculature to manipulations of the NO system is altered in the SNX rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of nifedipine on aortal cholesterol content, blood coagulation and elastin metabolism in cholesterol-fed rabbits.

Our studies showed that the nifedipine in daily doses of 30 mg/kg given to rabbits treated with a diet containing 1% cholesterol for 6 months, decreased cholesterol content in aorta homogenates, urine excretion of desmosines and prolonged partial thromboplastin time, while it did not alter serum lipids. These results may have some value for understanding of the antiatherogenic mechanism of nifedipine.

Thyrotropin stimulated colloid droplet formation in the thyroid of hypophysectomised mice after calcitonin administration.

The influence of calcitonin on colloid droplet formation in the thyroid gland of hypophysectomised mice after thyrotropin (TSH) stimulation was investigated. Calcitonin was injected 30 min before TSH administration. 30 min after TSH the colloid droplet index in the thyroid cells was twice as low in the calcitonin group in comparison with the control one (0.111 +/- 0.020, 0.228 +/- 0.025 respectively). 60 min after thyrotropin treatment the number of colloid droplets was higher in the animals treated with calcitonin (0.135 +/- 0.093) in comparison with the control group (0.083 +/- 0.025). The possible mechanism of calcitonin action on colloid droplet formation is discussed.

Changes in serum TSH level after intraventricular injection of various neuromediators in rats.

The influence of various neuromediators on pituitary TSH secretion in rats has been investigated. Noradrenaline 50 microgram/rat, dopamine 50 microgram/rat, serotonine-creatinine-sulphate 100 micogram/rat, gamma-aminobutyric acid 100 microgram/rat, pilocarpine 1 mg/rat, histamine 100 microgram/rat were administered into the lateral ventricle of the brain. All agents were dissolved in Parker's fluid. Two control groups of animals were given Parker's fluid and subjected to surgical manipulations, respectively. Plasma TSH level was estimated after 30 min by means of radioimmunoassay. The increase in the TSH level was observed after the injection of serotonine and noradrenaline (4.0 and 3.1 ng/ml, respectively) as compared with control group (0.7 ng/ml).

The effect of serotonin given into the lateral ventricle of the brain on serum TSH level in normal and thyroxine-blocked rats.

The effect of serotonin given into the lateral ventricle of the brain in rats was investigated. Serotonin was solved in artificial cerebrospinal fluid and administered in three doses: 250 microgram, 50 microgram, 10 microgram. Only the highest dose of serotonin caused a statistically significant increase in serum TSH level 0.5 h after the injection. The possible role of serotonin in the blocking mechanism of thyroid hormones on TSH secretion was also taken into consideration. 50 microgram of serotonin significantly strengthened the lowering effect of 1-thyroxine given 0.5 h before on serum TSH level.