Antoni Wystrychowski

Exposure of Pregnant Rats to Cigarette- Smoke Condensate Causes Glomerular Abnormalities in Offspring

Background: Higher blood pressure and albuminuria are found in offspring of mothers who smoke during pregnancy. Whether or not kidney development is affected by maternal smoking is unknown. Methods: Sprague-Dawley rats were randomly allocated to twice-daily cigarettesmoke and nicotine condensate (1 mg/kg) or vehicle at day 10 of pregnancy until delivery. Results: Exposed offspring did not differ from control offspring with respect to body weight, kidney weight, albuminuria, and creatinine clearance. Both male and female offspring had higher tail-plethysmographic blood pressures and lower mean glomerular volume, podocyte, mesangial-cell, and endothelial-cell number, compared to control offspring. Conclusions: The data document that prenatal exposure to cigarette-smoke condensate containing nicotine influences normal kidney development and could predispose to higher blood pressures later in life.

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.

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 and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion

Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (μmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation.