Amelioration of cisplatin-induced acute kidney injury by recombinant neutrophil gelatinase-associated lipocalin

We investigated the protective effect and mechanism of neutrophil gelatinase-associated lipocalin (NGAL) in a murine model of cisplatin-induced nephrotoxicity. Male Swiss-Webster mice were assigned to four groups (n?=?10 in each group). Control mice received vehicle only. Mice in the experimental group were given a single intraperitoneal injection of cisplatin (20?mg/kg) to induce nephrotoxicity, and were divided into three groups. The first group received 100?μL of saline only via tail vein at the time of cisplatin administration. The second group was given biologically active recombinant NGAL via tail vein (250?μg/100?μL solution). The third group was injected with a 250?μg/100μL solution of inactivated NGAL. After 4 days, we measured serum creatinine and urinary N-acetyl-β-d-glucosaminidase (NAG), and performed histologic studies. Biologically active NGAL significantly blunted the rise in serum creatinine (NGAL plus cisplatin 1.33?±?0.31 versus cisplatin alone 2.43?±?0.31?mg/dL, p?<?.001) as well as the increase in urine NAG (NGAL plus cisplatin 60.7?±?14.2 versus cisplatin alone 120.5?±?22.5 units/gm creatinine, p?<?.005). In addition, NGAL conferred a marked reduction in tubule cell necrosis and apoptosis (NGAL plus cisplatin 6.9?±?1.2 versus cisplatin alone 15.1?±?3.4 TUNEL positive nuclei per 100 cells, p?<?.001). These beneficial effects were completely abolished when heat-inactivated NGAL was administered instead of the biologically active form. Since induction of NGAL in kidney tubules is a known physiologic response to cisplatin, the pharmacologic use of NGAL to prevent cisplatin nephrotoxicity is likely to be safe and effective.     

Effect of percutaneous nephrolithotomy on renal functions in children: assessment by quantitative SPECT of 99mTc-DMSA uptake by the kidneys

Abstract

Objective: To determine the impact of percutaneous nephrolithotomy (PNL) on global and regional renal function in children. Methods: In total, 40 children (41 renal units) undergoing PNL were included in this prospective study. All patients were evaluated using quantitative single-photon emission computed tomography (QSPECT) with technetium-99?m-dimercaptosuccinic acid (^99mTc-DMSA) examinations before and 3 months after surgery. Results: The mean age was 9.5 years (range, 3–16), and the mean stone size was 3.4?cm (range, 2–6.5). Of the cases, 39 (95%) were managed as being stone-free after a single session of PNL. After additional treatment procedures, 40 (97.5%) of the cases were managed as being stone-free. Of the 41 renal units, new focal cortical defects on ^99mTc-DMSA scans were seen in 4 (9.7%) patients. Total relative uptake in the treated kidneys increased from 42.3% to 44.1%. The mean creatinine level before PNL was 1.18?±?0.45 (0.8–1.6)?mg/dL compared with 1.16 (0.7–1.5)?mg/dL by the end of the follow-up period (not statistically significantly different, p?>?0.05). Conclusions: PNL in children is a safe and feasible method for the maximal clearance of stones. QSPECT of ^99mTc-DMSA confirmed that renal function is preserved or even improved after percutaneous stone removal.     

Whortleberry protects kidney against the cisplatin-induced nephrotoxicity: an experimental study

Purpose: This study investigated the antioxidant effects of whortleberry against cisplatin-induced nephrotoxicity in rats.

Material and methods: This study included 48 female Sprague–Dawley rats weighing 263.68?±?8.29?g. The rats were divided into the following six groups, with eight rats in each group: control, ethanol control, whortleberry control, cisplatin control, 16?mg/kg cisplatin +100?mg/kg whortleberry, and 16?mg/kg cisplatin +200?mg/kg whortleberry groups. Biochemical analysis was performed by measuring total oxidant status and total antioxidant status, histopathological analysis was performed by calculating proximal and distal tubule areas (μm²), and immunohistochemical analysis was performed by determining anti-Caspase-3 immunostaining. Differences among the groups were examined using one-way analysis of variance, and p?Results: Cisplatin treatment decreased the total antioxidant status and increased the total oxidant status and Caspase-3 level. Moreover, it resulted in the dilatation, vacuolization and loss of tubular epithelial cells; and glomerular degeneration and edema in the kidney tissues (p?p?Conclusions: Our results indicate that the antioxidant effects of the whortleberry decrease cisplatin-associated nephrotoxicity.     

Evaluation of the protective effect of agmatine against cisplatin nephrotoxicity with 99mTc-DMSA renal scintigraphy and cystatin-C

Background: The aim of the current study was to investigate whether agmatine (AGM) has a protective effect against cisplatin-induced nephrotoxicity.

Materials and methods: Thirty-two rats were randomly divided into four groups: (1) Saline (control); (2) Cisplatin (CDDP; 7.5?mg/kg intraperitoneally); (3) Agmatine (AGM; 10?mg/kg intraperitoneally); (4) Cisplatin plus agmatine (CDDP?+?AGM). Agmatine was given before and two consecutive days after cisplatin injection. All the animals underwent renal scintigraphy with 99mTc-DMSA. The levels of serum creatinine, cystatin C, and blood urea nitrogen (BUN) were measured in addition to examination of the tissue samples with light microscopy. Acute renal injury was assessed with biochemical analyses, scintigraphic imaging, and histopathological evaluation.

Results: In the cisplatin group, the levels of BUN, creatinine, and cystatin C were significantly higher than that of the controls. Histopathological examination showed remarkable damage of tubular and glomerular structures. Additionally, cisplatin caused markedly decreased renal 99mTc-DMSA uptake. AGM administration improved renal functions. Serum creatinine, BUN, and cystatin C levels had a tendency to normalize and, scintigraphic and histopathological findings showed significantly less evidence of renal toxicity than those observed in animals receiving cisplatin alone.

Conclusions: Our data indicate that AGM has a protective effect against cisplatin-induced nephrotoxicity. Therefore, it may improve the therapeutic index of cisplatin. In addition, the early renal damage induced by cisplatin and protective effects of AGM against cisplatin nephrotoxicity was accurately demonstrated with 99mTc-DMSA renal scintigraphy.     

Prediction of residual total renal function before nephron-sparing surgery using99mTc-DMSA renal scintigraphy

Background Although radical nephrectomy is the standard treatment for renal cell carcinoma, nephron-sparing surgery is the preferred treatment in patients with a single functioning kidney. It is important before surgery to evaluate the level of residual renal function likely after the operation. In this study, we investigated the prediction of residual renal function, using technetium Tc 99m dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy, before nephron-sparing surgery for renal tumors. Methods Preoperative and postoperative evaluation of renal function was done in 11 patients with renal cell carcinoma or renal angiomyolipoma, using^99mTc-DMSA scintigraphy. Nine patients had renal cell carcinoma and 2 had renal angiomyolipoma. Partial nephrectomy was performed in 4 patients and surgical enucleation in 7 patients. Both the predicted total DMSA renal uptake rate prior to surgery and the actual postoperative total^99mTc-DMSA renal uptake rate were obtained. Endogenous creatinine clearance and serum creatinine levels were also obtained. Results There was a good relationship between the predicted and postoperative total^99mTc-DMSA renal uptake rates. The ratio of the postoperative total DMSA renal uptake rate to the predicted total^99mTc-DMSA renal uptake rate was 85% after partial nephrectomy, and 101% after surgical enucleation. There was also a significant correlation between the postoperative total^99mTc-DMSA renal uptake rate and creatinine clearance, and postoperative total^99mTc-DMSA renal uptake rate levels above 11.4% coincided with serum creatinine levels below 2.0 mg/dL. Conclusion Preoperative assessment with^99mTc-DMSA renal scintigraphy is clinically useful for predicting residual renal function after nephron-sparing surgery.     

Effect of free creatine therapy on cisplatin-induced renal damage

Cisplatin is one of the commonly used anticancer drugs and nephrotoxicity limits its use. The aim of this study is to investigate the possible protective effect of creatine supplementation on cisplatin-induced nephrotoxicity. Sixty male Sprague–Dawley rats were divided into three groups: Group I: Cisplatin (n?=?20) (7?mg/kg cisplatin intraperitoneal (i.p.) single dose), group II: Cisplatin?+?creatine monohydrate (n?=?20) (7?mg/kg cisplatin i.p. single dose and 300?mg/kg creatine p.o. daily for 30 days starting on first day of cisplatin injection), group III: Control group (n?=?20) (Serum physiologic, 2.5?mL/kg i.p.). Sacrifications were performed at first week and 30th day. Blood urea nitrogen (BUN) and serum creatinine levels, histopathological evaluation, mitochondrial deoxyribonucleic acid (mtDNA) common deletion rates, and body weights of rats were evaluated. A significant decrease in body weight, higher values of kidney function tests, histopathological scores, and mtDNA deletion ratios were observed in group I compared to control group at days 7 and 30 (p?p?=?0.931 and 0.084, respectively). Kidney function tests, histopathological scores, and mtDNA common deletion ratios were statistically better in group II than group I at 7th and 30th day (p?相似文献   

Poor renal uptake of99mtechnetium-dimercaptosuccinic acid and near-normal99mtechnetium-mercaptoacetyltriglycine renogram in nephronophthisis

Four patients with the clinical diagnosis of nephronophthisis are presented, all having a very poor renal uptake of^99mtechnetium-dimercaptosuccinic acid (^99mTc-DMSA) but clearly visualized kidneys on early images with^99mtechnetium-mercaptoacetyltriglycine and a normal or almost normal renogram. There was no difference between a young patient in an early stage of the disease and the other three patients with more advanced renal disease. In contrast, a patient with tubulointerstitial nephritis with uveitis had considerably better renal uptake of^99mTc-DMSA despite impaired renal function. We suggest that the specific tubular function defect in nephronophthisis might be the cause of the poor uptake of^99mTc-DMSA. We also recommend the method to support the clinical suspicion of nephronophthisis, even in the early stages of the disease.     

Effect of creatine and pioglitazone on Hk-2 cell line cisplatin nephrotoxicity

Cisplatin is a chemotherapeutic agent, which is used in the treatment of various solid organ cancers, and its main dose limiting side effect of cisplatin is nephrotoxicity. The aim of this study is to investigate the role of pioglitazone and creatine on cisplatin nephrotoxicity in vitro. Real-time cell analyzer system (RTCA) was used for real-time and time-dependent analysis of the cellular response of HK-2 cells following incubation with cisplatin and combination with creatine or pioglitazone hydrochloride. First, half-maximal inhibitory concentrations (IC50) of cisplatin, creatine and pioglitazone were calculated by RTCA system. Afterwards creatine and pioglitazone was administered with serial dilutions under RTCA system. IC50 dose for cisplatin was 7.69?M?×?10^?5 at 24th hour and 3.93?M?×?10^?6 at 48th hour. IC50 dose for pioglitazone was 1.61?M?×?10^?3 at 24th hour and 2.85?M?×?10^?4 at 48th hour. Although cells were treated the dose of 40,225?mM creatine, IC50 dose could not been reached. Neither pioglitazone nor creatine had additional protective effect in any dose. Consequently, beneficial effect of creatine and pioglitazone on cisplatin-induced cell death could not be found. Further studies and clinical trials are needed to evaluate the effect of different doses of these drugs in cisplatin-induced nephrotoxicity.     

Cisplatin-induced nephrotoxicity in mice: protective role of Leea asiatica leaves

Abstract

Cisplatin is a popular anticancer drug, but its side effects like nephrotoxicity and hepatotoxicity due to oxidative stress limited its clinical use. In tis study, nephoprotective effect of fractions of Leea asiatica (Leeaceae) leaves was assessed against cisplatin induced toxicity in rats. Leaves of L. asiatica extracted with methanol, ethyl acetate, petroleum ether, and evaluated for in vitro and ex vivo antioxidant activity using several assay models. Methanol extract showed better antioxidant effects, and contain higher amount of phenolic (77.75?±?0.87?mg GAE/g of dry material) and flavonoid compound (60.98?±?0.58?mg QE/g of dry material) compared with other extracts. Hance methanol extract was selected for further investigation and fractionated with methanol, ethyl acetate, petroleum ether. Protective effect of methanol extract and its fractions was evaluated against cisplatin (20?mg/kg, i.p.) induced nephrotoxicity. Pretreatment with methanol extract (150 and 300?mg/kg), and its fractions especially methanol, ethyl acetate fraction (75 and 150?mg/kg) significantly reduced blood urea nitrogen, serum creatinine, uric acid levels, and decreased malondialdehyde level and increase total protein and albumin level (p?<?0.05, 0.01). Ethyl acetate fraction produced highest nephroprotective, possibly by inhibiting lipid peroxidation process. Result suggested that ethyl acetate fraction possesses potent nephroprotective activity and can be used an adjunct therapy aiming to improve the effectiveness of several nephrotoxic drugs.     

Curcumin counteracts cisplatin-induced nephrotoxicity by preventing renal tubular cell apoptosis

Curcumin has several biological functions particularly antioxidant and anti-inflammatory. The aims of this study are determination of the protective effects of curcumin on cisplatin-induced renal tubular cell apoptosis and related pathways in kidney. Eighteen male Wistar albino rats were randomly divided into three groups (n?=?6): the control, cisplatin (CP), and cisplatin?+?curcumin (CP?+?CUR). Acute renal damage was induced by single dose of cisplatin (7.5?mg/kg) injected by intraperitoneally (i.p). The animals of curcumin-treated group were received daily 200?mg/kg curcumin per os (po), starting from 2 days before the injection of cisplatin to the day of sacrifice. Forty-eight hours after cisplatin injection, samples of cardiac blood and kidneys were harvested from the animals. In this study, the major finding is that curcumin treatment ameliorates the following conditions associated with cisplatin-induced nephrotoxicity: (1) the development of kidney injury (histopathology), (2) inflammatory responses [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, IL-10 levels], (3) the degree of lipid peroxidation [malondialdehyde (MDA) level], (4) renal tubular cell apoptosis (active caspase-3) and expression of related proteins [p53, Fas, and Fas ligand (Fas-L)] by immunohistochemistry, (5) renal dysfunction (serum urea and creatinine). In a conclusion, this study suggests that curcumin has antiapoptotic effect against cisplatin nephrotoxicity, in addition to anti-inflammatory and antioxidant properties.     

Potential of morin and hesperidin in the prevention of cisplatin-induced nephrotoxicity

Oxidative stress is one of the important mechanisms of cisplatin-induced nephrotoxicity. Therefore, this study was designed to explore the potential protective effects of morin and/or hesperidin on oxidative stress in cisplatin-induced nephrotoxicity. This study was performed on 42 Wistar rats. Rats were divided into seven groups: control, morin, hesperidin, cisplatin, cisplatin?+?morin, cisplatin?+?hesperidin, and cisplatin?+?morin?+?hesperidin. Morin and/or hesperidin were given for 10 consecutive days by oral gavage and on the 4th day a single dose of cisplatin (7?mg/kg) was injected intraperitoneally. After administrations, on the 11th day of the experiment the animals were killed, and malondialdehyde (MDA), nitric oxide (NOx), glutathione (GSH) levels and myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD) activity were measured. Cisplatin-treated rats showed increased levels of MDA, and decreased levels of NOx also activity of CAT. Morin and/or hesperidin pretreatment prevent oxidative stress in kidney tissue, while they increase the NOx level, CAT activity, and decrease MPO activity. In conclusion, morin?+?hesperidin pretreatment may have a significant potential for protection of cisplatin-induced nephrotoxicity.     

Experimental study on effects of deferoxamine mesilate in ameliorating cisplatin-induced nephrotoxicity

Purpose: Cisplatin (CCDP), an indispensable agent of several chemotherapy protocols, has serious dose limiting side effects, including nephrotoxicity. In this experimental study, we used deferoxamine mesilate (DFO), an iron chelating agent, to ameliorate cisplatin-induced nephrotoxicity. Materials and methods: Sixty adult male bulb-c mice were divided in 6 equal groups. Group 1 received distilled water, group 2 received 100 mg/kg DFO, group 3 received 0.9 mg/kg CCDP, group 4 received 100 mg/kg DFO one hour before 0.9 mg/kg CCDP, group 5 received 1.8 mg/kg CCDP, and group 6 received 200 mg/kg DFO one hour before 1.8 mg/kg CCDP transperitoneally for 10 days. The next day, blood and urine samples were obtained, and all the animals were sacrificed, the kidneys and testes were removed, and histopathologic and biochemical analyses were performed. Results: Low-dose and high-dose CCDP treated mice had significantly more extensive proximal tubular degeneration (p < 0.001) when compared to control animals. Moreover, these changes were significantly less extensive in the mice taking DFO than mice taking CCDP. DFO showed no effect on cisplatin induced testicular histopathology. The cisplatin administration significantly increased the serum urea and plasma creatinin concentrations, and DFO administration prior to CCDP significantly decreased serum urea and plasma creatinin concentrations. Conclusion: Our findings suggest that DFO administration may be safe and useful for ameliorating cisplatin-induced nephrotoxicity.     

A Prospective Randomized Controlled Trial of the Metabolic Effects of Sleeve Gastrectomy with Transit Bipartition

Purpose

To compare the effects of the sleeve gastrectomy with transit bipartition (SG?+?TB) procedure with standard medical therapy (SMT) in mildly obese patients with type II diabetes (T2D).

Methods

This is a prospective, randomized, controlled trial. Twenty male adults, ≤?65 years old, with T2D, body mass index (BMI)?>?28 kg/m² and <?35 kg/m², and HbA1c level?>?8% were randomized to SG?+?TB or to SMT. Outcomes were the remission in the metabolic and cardiovascular risk variables up to 24 months.

Results

At 24 months, SG?+?TB group showed a significant decrease in HbaA1c values (9.3?±?2.1 versus 5.5?±?1.1%, P?=?<?0.05) whereas SMT group maintained similar levels from baseline (8.0?±?1.5 versus 8.3?±?1.1%, P?=?NS). BMI values were lower in the SG?+?TB group (25.3?±?2.8 kg/m² versus 30.9?±?2.5 kg/m²; P?=?<?0.001). At 24 months, none patient in SG?+?TB group needed medications for hyperlipidemia/hypertension. HDL-cholesterol levels increased in the SG?+?TB group (33?±?8 to 45?±?15 mg/dL, P?<?0.001). After 24 months, the area under the curve (AUC) of GLP1 increased and in the SG?+?TB group and the AUC of the GIP concentrations was lower in the SG?+?TB group than in the SMT. At 3 months, SG?+?TB group showed a marked increase in FGF19 levels (74.1?±?45.8 to 237.3?±?234 pg/mL; P?=?0.001).

Conclusions

SG?+?TB is superior to SMT and was associated with a better metabolic and cardiovascular profile.

     

The renoprotective effect of curcumin in cisplatin-induced nephrotoxicity

Abstract

The polyphenol curcumin has several pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer features. In this study, we evaluated the effects of curcumin in cisplatin-induced nephrotoxicity in rats. Male Wistar rats were divided into four groups: (1) control; (2) cisplatin (7?mg/kg body weight, intraperitoneal as a single dose); (3) curcumin (100?mg/kg via gavage, for 10 days); and (4) cisplatin and curcumin. The cisplatin-treated rats exhibited kidney injury manifested by increased serum urea and creatinine (p?<?0.05). The kidney tissue from the cisplatin treated rats also exhibited a significant increase in the malondialdehyde (MDA) levels (p?<?0.05). The treatment with curcumin prevented a rise in the serum urea, creatinine and MDA levels when compared to the control group kidneys (p?<?0.05). The analysis the nicotinamide phosphoribosyltransferase (NAMPT) and sirtuin (SIRT) proteins (SIRT1, SIRT3 and SIRT4), which play important roles in the resistance to stress and the modulation of the threshold of cell death, showed similar trends (p?<?0.05). In the cisplatin-only treated rats, the induced renal injury decreased the levels of the NAMPT and SIRT proteins. Conversely, the curcumin increased the levels of the NAMPT and SIRT proteins in the cisplatin-treated rats (p?<?0.05). These data suggest that curcumin can potentially be used to reduce chemotherapy-induced nephrotoxicity, thereby enhancing the therapeutic window of cisplatin.     

Renoprotective Effect of Spirulina fusiformis on Cisplatin-Induced Oxidative Stress and Renal Dysfunction in Rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidences have implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Spirulina fusiformis, blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of Spirulina fusiformis against cisplatin-induced oxidative stress and renal dysfunction. Spirulina fusiformis (500,1000,1500 mg/kg^?1 p.o.) was administered 2 days before and until 3 days after cisplatin challenge (5 mg/kg^?1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and by enzymatic activity of superoxide dismutase and catalase. A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic Spirulina fusiformis treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of Spirulina fusiformis in cisplatin-induced nephrotoxicity.     

Evaluation of Renoprotective Effect of Aphanizomenon flos-aquae on Cisplatin-Induced Renal Dysfunction in Rats

Cisplatin is an effective chemotherapeutic agent used in the treatment of a wide array of both pediatric and adult malignancies. Dose-dependent and cumulative nephrotoxicity is the major toxicity of this compound, sometimes requiring a reduction in dose or discontinuation of treatment. Recent evidence has implicated oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Aphanizomenon flos-aquae (AFA), blue-green algae, is claimed to be a potential antioxidant. The present study was designed to explore the renoprotective potential of AFA against cisplatin-induced oxidative stress and renal dysfunction. The ethanolic extract of Aphanizomenon flos-aquae (EEAFA) (25, 50, 100 mg/kg^?1 p.o.) was administered two days before through three days after cisplatin challenge (5 mg/kg^?1 i.p.). Renal injury was assessed by measuring serum creatinine, blood urea nitrogen, creatinine and urea clearance, and serum nitrite levels. Renal oxidative stress was determined by renal TBARS levels, reduced glutathione levels, and enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione transferase (GST). A single dose of cisplatin produced marked renal oxidative and nitrosative stress and significantly deranged renal functions. Chronic EEAFA treatment significantly and dose-dependently restored renal functions, reduced lipid peroxidation, and enhanced reduced glutathione levels, superoxide dismutase, and catalase activities. The results of the present study clearly demonstrate the pivotal role of reactive oxygen species and their relation to renal dysfunction and point to the therapeutic potential of AFA in cisplatin-induced nephrotoxicity.     

Decreased renal uptake of <Superscript>99m</Superscript>Tc-DMSA in patients with tubular proteinuria

Although technetium-99m-dimercaptosuccinic acid (^99mTc-DMSA) renal scans are widely used to evaluate renal tubular mass function, the mechanism by which renal uptake of DMSA occurs is still the subject of debate. Patients with various proximal tubular disorders show markedly decreased renal DMSA uptake, even when there is normal creatinine clearance. We measured the renal uptake of ^99mTc-DMSA 3 h after its injection in 13 patients with Dent disease or Lowe syndrome, both of which are typical proximal tubular disorders with defective megalin and cubilin-mediated endocytosis. Serial images of three patients were also obtained at 0.5, 1, 2 and 3 h post-injection. The correlations between renal uptake of ^99mTc-DMSA and creatinine clearance and the degrees of acidemia and tubular proteinuria were then evaluated. The renal uptake of ^99mTc-DMSA was markedly decreased in all patients, and the decreased uptake was detected in all serial images. In contrast, bladder radioactivity was higher than normal in all of the serial images when compared to renal radioactivity. Additionally, the uptake of ^99mTc-DMSA was inversely proportional to the amount of urine β₂-microglobulin. These results strongly suggest that DMSA is filtered in the glomeruli and subsequently undergoes megalin- and cubilin-mediated endocytosis in the proximal tubules.     

The incidence of cisplatin nephrotoxicity post hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery

Background: Cisplatin is commonly used in hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of peritoneal carcinomatosis. Little is known about the nephrotoxic effects of cisplatin use in HIPEC. Objectives: To report the incidence of nephrotoxicity post-HIPEC using cisplatin 50?mg/m² plus doxorubicin 15?mg/m². The incidence of hypomagnesemia was investigated as a secondary endpoint. Methods: This is a retrospective study evaluating patients who received cisplatin with doxorubicin during HIPEC. RIFLE classification was used to assess the development of nephrotoxicity. Variables, such as comorbidities and nephrotoxic medications were obtained. Renal function parameters were also collected, including serum creatinine levels and serum magnesium levels at baseline and at days 3, 7 and 30 after HIPEC. Perioperative urine output (UO) was also recorded. Results: Fifty-three patients were identified. Based on the RIFLE classification, two patients (3.7%) developed acute kidney injury (AKI) following HIPEC with cisplatin. One patient met criteria for renal failure and progressed to chronic renal failure. The other patient had renal injury. Comparable mean creatinine levels were observed at baseline and on day 30 following HIPEC (p?>?0.05). The incidence of hypomagnesemia increased to 24.5% by day 7 (p?=?0.041) and 30.1% by day 30 (p?p?Conclusion: Nephrotoxicity can complicate HIPEC with cisplatin therapy and that permanent renal dysfunction may rarely occur. More attention to be directed toward monitoring magnesium levels after cisplatin use with HIPEC.     

Radionuclide Staging of Renal Function in Type 1 Diabetes Mellitus

Aim. The aim of this study was to assess renal function in different stages of type 1 diabetes mellitus by radionuclide methods. Additionally, glomerular and tubular functions were correlated with urinary albumin (UAER) and N-acetyl-β-D-glucosaminidase (NAGA) excretion rates. Patients and methods. Fifty-three patients with diabetes mellitus were classified into four groups: normoalbuminuric (NA, 18 patients), microalbuminuric (MiA, 12 patients), macroalbuminuric (MaA, 13 patients), and chronic renal failure group (CRF, 10 patients). Glomerular filtration rate (GFR) was estimated by diethylenetriamine pentaacetic acid-technetium 99m (^99mTc-DTPA) clearance rate while tubular function was calculated as a percentage of net injected activity fixed in both kidneys, 4 h after intravenous injection of dimercaptosuccinate acid-technetium 99m (^99mTc-DMSA). Additionally, ^99mTc-DTPA clearance was correlated with estimated GFR (eGFR) by using modified Modification of Diet in Renal Disease (MDRD) Study Group formula. Results. ^99mTc-DTPA clearance and ^99mTc-DMSA fixation were found significantly higher in normoalbuminuric group (p < 0.05 and p < 0.02, respectively), unchanged in microalbuminuric group (p > 0.05, p > 0.05), and decreased in both macroalbuminuric (p < 0.0001, p < 0.00001) and chronic renal failure group (p < 0.0001, p < 0.00001). Renal function was denoted as normal, increased (hyperfunction), or decreased (hypofunction). It was found normal in a high percentage of patients with normalbuminuria (filtration 44.4%, fixation 72.2% pts) and microalbuminuria (66.7% and 66.7%). Renal hyperfunction was not only found frequent in normalbuminuric group (55.6% and 27.8%), but was also recorded in microalbuminuric group (8.3% and 8.3%). Renal hypofunction was present in all macroalbuminuric patients and in one-quarter of those with microalbuminuria as well. Such distribution of renal function conditions indicated normalbuminuric and microalbuminiric groups functionally heterogeneous. Regression analysis showed a significant correlation between ^99mTc-DTPA clearance and eGFR in MaA and CRF groups only. Although urinary NAGA excretion rate was shown as a less sensitive staging parameter, being significantly increased when compared to control group only in MaA and CRF groups (p < 0.05), it significantly correlated with ^99mTc-DTPA clearance rate (r = ?0.485, p = 0.0004) and ^99mTc-DMSA tubular fixation (r = ?0.526, p = 0.0002). Conclusions. The results of this study favor the performance of radionuclide studies together with the determination of urinary albumin excretion rate in patients with type 1 diabetes mellitus in order to achieve more reliable staging of diabetic kidney disease. The demonstration of glomerular hyperfiltration and tubular hyperfunction by radiopharmaceuticals contributes to the early detection of diabetic kidney disease, while the quantification of renal function enables the follow-up of the progressive function loss in the later course of the disease.     

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n?=?32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A?+?P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4?μg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2?g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A?+?P had lower mean fractional sodium excretion (p?<?0.001) as well as higher creatinine clearance (p?=?0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p?=?0.035) and serum 8-hydroxy-2′-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p?<?0.001) were significantly lower; superoxide dismutase (p?=?0.024) and glutathione peroxidase (p?=?0.007) activities of renal tissue were significantly higher in group A?+?P than in group A. The mean scores of tubular necrosis (p?=?0.024), proteinaceous casts (p?=?0.038), medullary congestion (p?=?0.035), and VEGF immunoexpression (p?=?0.018) were also lower in group A?+?P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.