N-ACETYLCYSTEINE AS SALVAGE THERAPY IN CISPLATIN NEPHROTOXICITY

N-acetylcysteine (NAC) repletes intracellular stores of reduced glutathione and may be a scavenger of oxygen free radicals. We report a 52-year-old female who developed acute renal insufficiency after administration of one dose of 150 mg of cisplatin for treatment of squamous cell cancer of the esophagus. Her blood urea nitrogen and creatinine rose from 12 and 0.7 mg/dL, respectively, to 24 and 1.8 mg/dL on day 5 after cisplatin. On that day the patient was begun on NAC, starting with a loading dose of 140-mg/kg-body weight followed by 70 mg/kg every 4 h for 4 days. Two days after starting NAC her renal function began to improve, and although she failed to complete a full course of the drug, by day 10 her serum creatinine had fallen to 0.8 mg/dL. A previous report showed that N-acetylcysteine might reverse cisplatin-induced renal toxicity. Our case supports this hypothesis.     

N-acetylcysteine attenuates kidney injury in rats subjected to renal ischaemia-reperfusion.

BACKGROUND: The aim of the present study is to examine the effects of N-acetylcysteine (NAC), a thiol-containing anti-oxidant, on renal function and morphology, and biomarkers of oxidative stress, in rats subjected to renal ischaemia-reperfusion (IR). METHODS: Sprague-Dawley rats underwent unilateral nephrectomy and either contralateral renal IR (40 min of renal arterial clamping), or sham manipulation. Treatment groups were: (1) IR-Saline, (2) IR-NAC, (3) Sham-Saline and (4) Sham-NAC. The N-acetylcysteine was administered in a dose of 200 mg/kg intraperitoneally at 24, 12 and 2 h before, and 24, 48 and 72 h after, renal IR. Plasma creatinine was measured on days 1, 3 and 7 after IR, and kidney histology was assessed on day 7. In separate groups of animals we measured renal levels of the anti-oxidant glutathione, markers of systemic oxidative stress (plasma ascorbyl radical, urinary 8-iso-prostaglandin F2alpha), and glomerular filtration rate (GFR) by 51Cr-EDTA clearance, on day 1 after renal IR. RESULTS: Treatment with NAC ameliorated the decline in GFR and reduced hyperkalaemia on day 1 (P<0.05), lowered plasma creatinine levels on days 1 and 3 (P<0.05), and decreased renal interstitial inflammation on day 7 (P<0.05), after renal IR. Kidney glutathione levels decreased significantly in group IR-Saline in response to IR (P<0.05), but were completely repleted in group IR-NAC. Groups with renal IR injury and acute renal failure showed increased plasma ascorbyl radical levels, and elevated urinary 8-iso-prostaglandin F2alpha excretion, compared with sham (P<0.05). N-acetylcysteine treatment reduced plasma ascorbyl concentrations 24 h after renal IR (P<0.05), but had no effect on the rate of urinary 8-iso-prostaglandin F2alpha excretion. CONCLUSIONS: N-acetylcysteine improves kidney function, and reduces renal interstitial inflammation, in rats subjected to renal IR. These effects were associated with increased renal glutathione levels, and decreased plasma ascorbyl concentrations, suggesting that NAC attenuates renal and systemic oxidative stress in this model.     

Effect of N-acetylcysteine on renal function in patients with chronic kidney disease

BACKGROUND: N-acetylcysteine (NAC) is commonly administered to high-risk individuals to attenuate the risk of contrast-induced nephropathy in spite of the debate regarding its efficacy. In several studies serum creatinine decreased after exposure to NAC and contrast dye. The mechanism by which NAC attenuates the decline in renal function is not known. Studies in subjects with normal renal function suggest NAC may have an effect on tubular secretion. AIM: The aim of this study was to determine the effect of NAC on renal function, measured by serum creatinine and Cystatin C, in patients with stage 3 chronic kidney disease. METHOD: Serum creatinine and Cystatin C were measured prior to, 4, 24 and 48 h after the administration of 600 mg oral NAC in 30 patients. The protocol was repeated with the addition of 1200 mg oral cimetidine administered 3 h before NAC. RESULTs: Serum creatinine was not significantly different from baseline (186 +/- 65 micromol/L) to 4 h (185 +/- 62 micromol/L), 24 h (187 +/- 64 micromol/L) or 48 h (184 +/- 61 micromol/L) post NAC, nor were Cystatin C levels. Co-administration of cimetidine resulted in a significant rise in serum creatinine with no change in Cystatin C levels. CONCLUSION: This study failed to detect a change in serum creatinine or Cystatin C after a single dose of NAC in participants with stage 3 chronic kidney disease. Further randomized trials of multiple doses and longer follow up are needed to confirm these results.     

A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction after cardiac angiography. Recently, N-acetylcysteine (NAC) has been found to reduce the risk of CN after CT imaging with contrast enhancement. The purpose of the current study was to evaluate the efficacy of NAC for the prevention of CN in the setting of cardiac angiography. METHODS: Eligible patients were those undergoing cardiac angiography with serum creatinine>1.7 mg/dL. Patients were randomized to one of two groups: Group 1, IV hydration and NAC, 1200 mg one hour before angiography, and a second dose 3 hours after; Group 2, IV hydration and placebo. CN was defined as an increase of 0.5 mg/dL in serum creatinine. RESULTS: Seventy-nine patients completed the study. There were no significant differences between the groups in baseline characteristics, duration of angiography, mean volume of dye infused or mean IV hydration. Contrast nephropathy developed in 24.0% of subjects, 26.3% NAC, and 22.0% placebo (P = NS). Among subjects with diabetes mellitus, there was no significant difference in the rate of CN between the groups (42.1% NAC, 27.8% placebo; P = 0.09). The independent predictors of CN risk were diabetes mellitus and preexisting chronic renal insufficiency. CONCLUSIONS: NAC was not effective for the prevention of CN after cardiac angiography.     

Nephrotic Syndrome and Acute Tubular Necrosis Due to Meloxicam Use

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used by patients all over the world. Five to eighteen percent of the patients who receive NSAIDs can suffer from kidney-related side effects. Among them, the most relevant are sodium and water retention, hyponatremia, worsening of hypertension or preexisting cardiac failure, hyperkalemia, acute kidney injury, chronic kidney disease, papillary necrosis, nephrotic syndrome (NS), and acute interstitial nephritis. We report the case of a 65-year-old woman who developed acute tubular necrosis and NS a few days after receiving 15 mg of meloxicam (MLX) for 3 days for tendinitis. Steroid therapy was begun with normalization of kidney function after 7 weeks of treatment. NS (minimal change disease) was characterized by frequent remissions and relapses as prednisone was lowered under 30 mg/day. Azathioprine (100 mg/day) was added on the fifth month of diagnosis and a complete remission was finally obtained 4 years after hospital admittance. In her last medical checkup, 8 years after her debut and receiving azathioprine (50 mg) and prednisone (5 mg/day), renal function was normal (creatinine 1.0 mg/dL and creatinine clearance 80 mL/min/1.73 m²), proteinuria was 150 mg/day and there was no hematuria or hypertension.

The aim of communicating this case is to raise a warning about these renal side effects of MLX. After thorough review of literature, only one other report with the same findings was found.     

Attenuation of ischemia-reperfusion injury in a canine model of autologous renal transplantation

BACKGROUND: This study examined the potential therapeutic effects of a combination therapy consisting of 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) and N-acetyl cysteine (NAC) to attenuate ischemia-reperfusion (I/R) injury in a canine model of autologous renal transplantation. METHODS: Male mongrel dogs (15-20 kg) underwent left nephrectomy followed by flushing and static preservation of the kidney in University of Wisconsin (UW) solution for 48 hr. The treatment group received AICAR (50 mg/kg) plus NAC (100 mg/kg) intravenously before the left nephrectomy. The compounds were added to the UW solution as well. All dogs underwent right nephrectomy 48 hr later followed by autotransplantation of the preserved left kidney. Treated dogs received a second dose of AICAR and NAC before implantation of the renal autograft. RESULTS: The treated dogs had excellent urine output posttransplant, with peak serum creatinine of 7.26 mg/dL on postoperative day (POD) 3 that normalized after 14 days. The control group were anuric and developed clinical symptoms of uremia on POD 1. Morphologic evaluation supported the protective effects of combination therapy. Immunohistochemical analysis revealed decrease of tumor necrosis factor-alpha, interferon-gamma, and inducible nitric oxide synthase; and TUNEL assay showed decreased apoptosis in the treated group. CONCLUSIONS: Combination therapy with AICAR and NAC attenuates renal I/R injury and improves the outcome of the transplanted kidney after prolonged cold preservation.     

Nephrotoxicity of low-osmolality versus iso-osmolality contrast agents: impact of N-acetylcysteine

BACKGROUND: Recent data support that iodixanol, an iso-osmolality contrast agent, is less nephrotoxic than low-osmolality contrast agents when hydration is the only prophylactic strategy used. We evaluated the nephrotoxicity of iso- and low-osmolality contrast agents with prophylactic administration of N-acetylcysteine (NAC) along with hydration. METHODS: Two hundred and twenty-five patients with chronic renal insufficiency (serum creatinine >1.5 mg/dL or an estimated glomerular filtration rate <60 mL/min/1.73 m(2)), referred to our institution for coronary and/or peripheral procedures, were assigned to receive low-osmolality (iobitridol group; N = 115) or iso-osmolality (iodixanol group; N = 110) contrast dye. In all cases prophylactic administration of 0.45% saline intravenously and NAC (1200 mg orally twice daily) was used. RESULTS: Baseline creatinine levels were similar in the 2 groups [iobitridol group = 1.70 (IQR: 1.54-1.98) mg/dL; iodixanol group = 1.73 (IQR: 1.56-2.00) mg/dL, P = 0.33]. The risk score for contrast nephrotoxicity was 5.0 +/- 1.6 in the iobitridol group versus 5.0 +/- 1.8 in the iodixanol group (P = 0.44). Increase of at least 0.5 mg/dL of the creatinine concentration 48 hours after the procedure occurred in 4/115 patients (3.5%) in the iobitridol group and 3/110 patients (2.7%) in the iodixanol group (P = 1.00; OR 0.78; 95% CI 0.17-3.56). Amount of contrast media administration was similar in the 2 groups (iobitridol group = 167 +/- 90 mL; iodixanol group = 164 +/- 82 mL; P = 0.61). CONCLUSION: Nephrotoxicity of iso-osmolality and low-osmolality contrast agents was similar when a prophylactic strategy of hydration plus NAC was utilized.     

Effects of dexpanthenol and N-acetylcysteine pretreatment in rats before renal ischemia/reperfusion injury

Background: We investigated the anti-inflammatory and protective effects of concomitant use of dexpanthenol (DXP) and N-acetylcysteine (NAC) induced ischemia/reperfusion (I/R) injury of kidney. Methods: Forty rats were randomly divided into 5 groups. In all groups except for Group 1(Sham), renal arteries bilaterally occluded with vascular clamp for IR injury. Group 1(Sham), received a single dose of 10?mL/kg isotonic saline daily by intraperitoneal (IP) injection for three days. Group 2(IR), received a single dose of 10?mL/kg isotonic saline daily by IP injection for three days. Group 3(IR?+?NAC), received 300?mg/kg NAC daily by IP injection for three days. Group 4(IR?+?DXP), received 500?mg/kg DXP daily by IP injection for three days. Group 5(IR?+?NAC?+?DXP), received 500?mg/kg DXP and 300?mg/kg NAC daily by IP injection for three days. Serum urea (BUN), creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2, siderocalin) levels were measured as kidney function tests. TNF-α levels were measured as inflammatory marker. Tissue sections were evaluated histopathologically under light microscopy. Results: IR?+?NAC?+?DXP group received both NAC and DXP before induction of renal I/R and as the biochemical and histopathological data revealed the results of the IR?+?NAC?+?DXP group and sham group were similar. Biochemically and histopathologically, combined use of NAC and DXP has better results when each of them used alone. Conclusion: We concluded that concomitant use of DXP and NAC plays a major role against I/R injury and may be useful in acute treatment of I/R induced renal failure.     

Acute renal dysfunction in acetaminophen poisoning

Although acetaminophen (APAP)-associated liver injury is well recognized, there are few reports describing APAP nephrotoxicity, and most of them are single cases. It has also been suggested that N-acetylcysteine (NAC), used to treat the hepatotoxicity, may be harmful to the kidneys. To examine this contention and to determine whether renal involvement in APAP poisoning is at all common, we analyzed the incidence and outcome of acute renal dysfunction in patients hospitalized for APAP overdose reported to our regional poison center over a year. Eleven APAP-poisoned patients had elevated liver function tests; nine of them had azotemia. Those with higher AST levels tended to be younger and to have lower APAP levels on admission. Two patients with acute renal injury died after admission. The other seven patients with renal dysfunction recovered in 2 to 7 days. Six of these received NAC; their mean serum creatinine fell from 3.2 +/- 2.0 versus 1.7 +/- 0.9 mg/dL (p < 0.05). We conclude that acute renal failure is not uncommon in APAP poisoning and appears to be unrelated to the degree of liver injury. NAC therapy did not seem to worsen nephrotoxicity.     

Effects of N-acetylcysteine on myoglobinuric-acute renal failure in rats

Oxygen metabolites play an important role in renal injury during myoglobinuric acute renal failure (ARF). This study was designed to determine the protective influence of N-acetylcysteine (NAC), a hydroxyl radical scavenger, and treatment in an experimental model of myoglobinuric-ARF induced by intramuscular injection of hypertonic glycerol in rats. The rats were randomly distributed into five groups: Group 0 (n = 10), was assigned to receive 2mL saline (0,9%) intraperitoneally (ip); Group 1 (n = 10), NAC ip in a dose of 0 mg/100 g of body weight 30 min before the intramuscular (im) injection of 50% glycerol (10 mg/kg); Group 2 (n = 10), received saline 0,9% ip in a equivalent volume of NAC in Group I before the im injection of glycerol; Group 3 (n = 10), received NAC ip in a dose of 10 mg/100 g after im injection of glycerol; Group 4 (n = 10), saline 0,9% ip in a equivalent volume of NAC of the Group 3 after im administration of glycerol. After 24 h rats were sacrificed and kidney morphology and renal function were determined. A severe renal failure was produced by glycerol injection in the Groups 1, 2, 3, and 4, with significant tubular proximal necrosis and cast formation, and creatinine and urea concentrations were elevated in these groups without significant differences among groups, but Group 0 where the values were significantly lower. The results of this study suggests that ip administration of NAC in rats before or after glycerol injection do not confer protection against impairment of renal function under these conditions in this model of myoglobinuric-ARF.     

N-acetylcysteine attenuates NSAID-induced rat renal failure by restoring intrarenal prostaglandin synthesis.

BACKGROUND: Renal failure is a threatening side-effect of NSAID administration, consequent to NSAID-mediated abrogation of prostaglandin synthesis and resultant renal ischaemia. N-acetylcysteine (NAC) has renoprotective properties. We examined effects of NAC in a rat model of NSAID-induced renal failure. METHODS: Renal failure was generated in 80 rats by 6-day water deprivation and 3-day 15 mg/kg/day diclofenac injection. The rats were concomitantly treated, or not, by NAC, 40 mg/kg/day. Renal function was evaluated by cystatin C, creatinine and urea. Intrarenal blood flow was measured by laser Doppler. The kidneys were subjected to pathological examination or evaluation of intrarenal NO, H2O2 and PGE2. RESULTS: NAC significantly attenuated deterioration of renal function in diclofenac-treated rats: cystatin C dropped from 2.8+/-0.35 to 2.2+/-0.67 mg/l, P=0.016; creatinine from 1.2+/-0.97 to 0.96+/-0.19 mg/dl, P=0.02; urea from 208.4+/-57.9 to 157.6+/-33.7 mg/dl, P=0.028. Diclofenac-inflicted hystopathological damage was significantly reduced following NAC treatment. Intrarenal medullar blood flow dropped by 51+/-12.4% in diclofenac-treated rats, but only by 14+/-3.39% in those receiving NAC after diclofenac injection (P<0.001). H2O2 was elevated in renal tissues of diclofenac-receiving rats, while decreased in NAC-treated animals. PGE2 release by diclofenac-treated rats dropped significantly, but was restored after NAC administration both in renal cortices (144.7+/-10.4 vs 19.7+/-1.5 pmol/ml, P<0.001) and medullae (148.5+/-7.3 vs 66.6+/-7.3 pmol/ml, P<0.001). CONCLUSIONS: In this model of renal failure induced by NSAID administration combined with water deprivation, NAC treatment successfully attenuated the deterioration of renal function by inducing renal vasodilatation, decreasing oxidative stress via inhibition of intrarenal ROS content and restoration of intrarenal PGE2 release back to the basal levels.     

Protective action of glycine in cisplatin nephrotoxicity

Because glycine is cytoprotective for kidney cells in vitro, we investigated its possible action in vivo to protect rats against cisplatin nephrotoxicity, a well-established experimental model of renal tubular injury. Glycine was infused at a dose of 1 mmol per 100 g body weight per hour for 75 minutes, starting 15 minutes before cisplatin, 5 mg per kg, was injected intravenously. Plasma concentration of glycine rose to 3.5 mmol per liter at the time cisplatin was injected. These rats were compared with cisplatin-treated animals treated with L-alanine or with isotonic saline. After five days plasma creatinine of saline-treated rats given cisplatin had risen threefold to 2.6 +/- 1.5 mg per 100 ml (mean +/- SD), as creatinine clearance fell to 25% of baseline (0.14 +/- 0.05 ml/min/100 g). Morphological evaluation disclosed extensive damage involving all S3 segments in the outer medulla as well as the medullary rays of the cortex. In contrast, in rats treated with glycine, plasma creatinine rose only to 1.2 +/- 0.2 mg/100 ml and creatinine clearance was maintained at 75% of baseline (0.35 +/- 0.05 ml/min/100 g). Glycine also attenuated the weight loss, polyuria, increased fractional excretion of sodium and potassium, decreased urinary osmolality, and renal glycosuria observed in control, saline-treated rats after cisplatin, while substantially decreasing the percentage of S3 tubules with evident morphological injury. Renal platinum content was unaffected by glycine. The administration of L-alanine or the delayed infusion of glycine, starting one hour after cisplatin was given, did not prevent cisplatin toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Kidney transplantation and enzyme alpha-galactosidase A therapy in patient with Fabry disease: a case report

Fabry disease, an X-linked recessive glycolipid storage disease, is caused by a deficiency of the lysosomal enzyme alpha-galactosidase A (alpha-Gal A), which cleaves a fatty substance called globotriaosylceramide (GL3). The abnormal storage of GL3 in blood vessel walls leads to ischemia and necrosis, particularly in blood vessels of the skin, kidneys, heart, brain, and nervous system. The aim of our study was to present the results of cadaveric kidney transplantation with enzyme alpha-Gal A therapy in a patient with Fabry disease. The patient was diagnosed with Fabry disease at the age of 33 years, based on enzymatic tests. Renal manifestations occurred a year later as proteinuria. At the age of 35 years, the glomerular filtration rate (GFR) was within the normal range. The patient received supplemental enzyme treatment with alpha-Gal (1 mg/kg every 2 weeks). At 3 months after starting supplementation, renal function worsened with serum creatinine levels at 1.7 to 1.8 mg/dL. The following months of supplementation (alpha-Gal 1 mg/kg) concurred with progressive renal dysfunction. After 27 months of supplementation at 37 years, with a creatinine value of 5.5 mg/dL, hemodialysis began and months later the patient received a cadaveric kidney graft. The patient no longer required dialysis. On postoperative day 5 the serum creatinine was 3.9 mg/dL; on day 7, 2.2 mg/dL; on day 14, 1.5 mg/dL. Enzyme supplementation began on posttransplant day 13. Renal graft function has been good during 5 months of observation with creatinine levels at 1.2 to 1.3 mg/dL. The treatment does not interfere with tacrolimus metabolism. Simultaneous chronic enzyme supplementation is the optimal treatment in the fifth stage of end-stage renal disease in Fabry disease.     

Crescentic glomerulonephritis associated with renal cell carcinoma after cancer immunotherapy

A 59 year-old woman showed rapidly progressive glomerulonephritis during immunotherapy for metastatic renal cell carcinoma. She received unilateral nephrectomy and cytotoxic T lymphocyte (CTL) therapy for the treatment of retroperitoneal lymph node metastasis of renal cell carcinoma. With CTL therapy, her retroperitoneal lymph node mass decreased in size. One year after the third round of CTL therapy, her serum creatinine was increased and massive proteinuria occurred. Her renal biopsy specimen revealed necrotizing and crescentic glomerulonephritis with immune complex deposition. Her retroperitoneal lymph node mass continued to decrease in size. Consequently, for the purpose of avoiding interfering with the CTL therapy, we performed double filtration plasmapheresis (DFPP) monotherapy for removal of immune complexes without using immunosuppressive drugs or prednisolone. After 24 sessions of DFPP, her serum IgG was reduced from 3,942 mg/dL to 2,400 mg/dL, and proteinuria (from 9.0 g/day to 0.9 g/day) and renal function (serum creatinine; from 5.6 mg/dL to 2.2 mg/dL) also improved. However, 3 months after the final DFPP, she expired due to perforation of the colon. The autopsy sample of the kidney showed that most of the glomeruli were obsolescent, but immunoglobulin depositions were reduced and necrotizing lesions were diminished. In the patients with RPGN associated with renal cell carcinoma, renal functional recovery has not been observed upon immunosuppressive treatment. Consequently, plasmapheresis is considered to be one of the effective and safe methods for patients with this association. We also discuss previous reports of RPGN associated with renal cell carcinoma, or RPGN after cancer immunotherapy.     

Beneficial effect of N-acetyl-cysteine on renal injury triggered by ischemia and reperfusion

Reactive oxygen species are critical mediators of the early phase of ischemic (IR) injury. The contribution of antioxidants, such as N-acetyl-cysteine (NAC), in ameliorating the parenchymal lesions, inflammatory parameters, and functional variables in renal IR is still controversial. We studied the effect of NAC administration on renal injury induced by IR. Mice were subjected to renal pedicle occlusion and subsequent reperfusion for 24 or 120 hours. NAC was administered prior to surgery at two concentrations (40 or 300 mg/kg, i.p.). Renal function and acute tubular necrosis were assessed, as well as immune phenotyping of infiltrating cells, by flow cytometry. At 40 mg/dL of NAC, we did not observe any significant improvement in renal function (1.85 +/- 0.43 md/dL, P = .367) or tissue architecture (% of ATN: 2.51 +/- 0.27 mm, P = .852) compared to the controls (1.87 +/- 0.43 mg/dL and 3.12 +/- 0.34 mm, respectively). However, animals that received 300 mg/dL of NAC showed lower serum creatinine values (24 hours: 1.25 +/- 0.54 mg/dL) compared to controls (P = .009) and less extensive acute tubular necrosis (1.54 +/- 0.12 vs, P < .05). Treatment with 300 mg/dL of NAC decreased renal dendritic cell infiltration. The protective effect of NAC was better observed at high concentrations and early times.     

Prevention of contrast-induced nephropathy in vascular patients undergoing angiography: a randomized controlled trial of intravenous N-acetylcysteine

OBJECTIVE(S): Apart from proper hydration, only oral N-acetylcysteine (NAC) has shown efficacy in reducing radiographic contrast media (RCM)-induced acute renal failure, though its benefit has been challenged. We investigated the effect of intravenous (i.v.) NAC on renal function in patients with vascular disease receiving RCM for angiography. METHODS: Single-center, randomized, double-blind, placebo-controlled trial. Based on a previous study, a trial with 44 patients each in placebo and treatment arms would give at least 80% power to show a statistically significant difference at the 5% level. Vascular patients undergoing angiography were consented and segregated into those whose serum creatinine (SC) level was normal or raised (men >1.32 mg/dl; women >1.07 mg/dL). All patients received 500 mL i.v. normal saline 6 to 12 hours prior to and then after angiography. Groups with normal SC and raised SC were randomly assigned to either 1 g of NAC with normal saline before and after angiography or nothing (placebo). Main outcome measures were change in SC and creatinine clearance (CrCl) as measured 1, 2, and 7 days postangiography (with comparison between active and placebo groups using unpaired t test) and incidence of acute renal decline (>25% or 0.5 mg/dL rise in SC) at 48 hours (with comparison between active and placebo using the Fisher exact test). RESULTS: Forty-six patients received NAC (29 normal SC, 17 raised SC), and 48 received placebo (27 normal SC, 21 raised SC). There was no significant difference in postangiography SC or CrCl at any of the time points measured between NAC and placebo in patients with either normal or raised SC. In the raised SC group, 3 patients from both the NAC and placebo groups suffered acute renal declines. Importantly, at 48 hours, the impaired SC group had a significant reduction in CrCl (-14% +/- 41% vs +18% +/- 58%: P = .0142) and a significant rise in SC (+7.0 +/- 25% vs -1.6% +/- 10%; P = .0246) when compared with the normal SC group. CONCLUSIONS: NAC (i.v. at 1 g) precontrast and postcontrast does not confer any benefit in preventing RCM-induced nephropathy in vascular patients. Patients with pre-existing raised SC have an increased risk of renal impairment as defined by a fall in CrCl and a rise in SC post-RCM when compared with patients with normal SC who appear to benefit from hydration.     

Improved estimation of glomerular filtration rate by serum cystatin C in preventing contrast induced nephropathy by N-acetylcysteine or zinc--preliminary results.

BACKGROUND: Prevention of contrast media (CM) induced nephropathy (CIN) by prophylaxis (e.g. N-acetylcysteine; NAC) is controversially discussed. Up to now, assessment of kidney function has been based on measurements of serum creatinine, although this biomarker has several limitations. We investigated NAC and zinc (Zn) for the prevention of CIN by monitoring creatinine and cystatin C. METHODS: In a prospective, placebo-controlled, double blind trial, patients with moderately impaired kidney function receiving low-osmolar, non-ionic CM were randomly assigned to an oral treatment for 2 days with 1.2 g/day of NAC (n = 19), for 1 day with 60 mg/day of Zn (n = 18) or placebo (n = 17). All patients received peri-procedurally 1 ml/kg/h of 0.45% saline for 24 h. At baseline, prior to exposure of CM, 2 and 6 days after CM, creatinine and cystatin C were measured. RESULTS: There was no difference in the incidence of CIN, but a significant drop in creatinine (P < 0.05) was observed in all patients during volume expansion. Creatinine showed no increase after CM and it was normalized to the baseline values in all groups at the study end. In contrast, 2 days after CM there was a significant rise in cystatin C in the Zn (P = 0.012) and the placebo (P = 0.041) group, whereas NAC prevented this deterioration of kidney function. CONCLUSIONS: Cystatin C seems to reflect CM-induced changes in kidney function better than creatinine. NAC and Zn have no effect in preventing CIN by the standard definition, but based on cystatin C we can confirm a preventive effect of NAC. It appears mandatory to assess kidney function by cystatin C in CIN intervention trials, because relying on creatinine can be misleading.     

Protective effect of N-acetylcysteine on early outcomes of deceased renal transplantation

We investigated the effects of the antioxidant N-acetylcysteine (NAC) on early outcomes of deceased donor renal transplantation. Between April 2005 and June 2008, adult primary graft recipients of deceased renal donors were assigned to treatment (n = 38) or control (n = 36) groups and evaluated for 90 days and one year after renal transplantation. The treatment group received NAC orally (600 mg twice daily) from day 0 to 7 postoperatively. Renal function was determined by serum creatinine, MDRD and Cockcroft-Gault estimated GFR (eGFR), delayed graft function (DGF) and dialysis free Kaplan-Meier estimate curve. Serum levels of thiobarbituric acid reactive substances (TBARS), were employed as markers of oxidative stress. The NAC group displayed a lower mean serum creatinine during the first 90 days (P = .026) and at 1 year after transplantation (P = .005). Furthermore, the NAC group showed a higher mean eGFR throughout the first 90 days and at 1 year. DGF was lower among the NAC group (P = .017) and these recipients required fewer days of dialysis (P = .012). Oxidative stress was significantly attenuated with NAC (P < .001). Our results suggested that NAC enhanced early outcomes of deceased donor renal transplantation by attenuating oxidative stress.     

The grafted kidney takes over: disappearance of the nephrotic syndrome after preemptive pancreas-kidney and kidney transplantation in diabetic nephropathy

This report describes the rapid and complete reversal of proteinuria after preemptive transplantation in diabetic nephropathy. Case 1 was a 42-year-old woman with type 1 diabetes (before pancreas-kidney graft: serum creatinine 1.6 mg/dL and proteinuria 9.1 g/day; 1 month after pancreas-kidney graft: proteinuria 0.3 g/day and creatinine 1.3 mg/dL). Case 2 was a 48-year-old man with type 2 diabetes (before kidney graft: creatinine 2 mg/dL and proteinuria 5.9 g/day; 1 month after: proteinuria 0.7 g/day and creatinine 1.1 mg/dL). The proteinuria pattern changed (pre: glomerular nonselective, tubular complete; post: physiologic). Renal scintiscan (99mTC-MAG3) demonstrated functional exclusion of the native kidneys, despite high pretransplant clearance (> 50 mL/min). The effect was not linked to euglycemia or readily explainable by pharmacologic effects (no difference in renal parameters after pancreas transplantation with the same protocols). These data confirm the efficacy of preemptive kidney and kidney-pancreas transplantation in diabetic nephrotic syndrome and indicate that a regulatory hemodynamic effect should be investigated.     

Impairment of renal function following liver transplantation

BACKGROUND: Although renal insufficiency following liver transplantation is not infrequent, only limited reports describe the incidence and progression of the kidney disease. METHODS: This single-centre retrospective analysis after successful liver transplantation between January 1985 and March 2002 defined the baseline serum creatinine at 50 days after liver transplantation to represent the renal function. The primary end-point was an increase of serum creatinine by more than 50% above the baseline. RESULTS: Long-term data were available for 162 patients (84 women, 78 men) who received 167 liver transplants. The median serum creatinine level at 50 days after liver transplantation was 1.0 mg/dL (range 0.5-3.5 mg/dL). The median serum creatinine increased to 1.2 mg/dL (0.4-9.8 mg/dL) at the end of follow-up. Six patients (4%) experienced end-stage renal failure. Forty-one patients (25%) showed a 50% increase in the serum creatinine. Kaplan-Meier analysis revealed that 43% and 48% of patients had a deterioration of renal function at 10 and 15 years after liver transplantation, respectively. Patients at risk showed an increase of serum creatinine by 0.25 mg/dL/y. Only the recipient age was an independent risk factor for deterioration of renal function. CONCLUSIONS: Although there is a high risk for the impairment of renal function after liver transplantation, progression of renal disease is slow and rarely results in end-stage renal failure within 10-15 years. However, patients at risk should be identified early to prevent further decline in renal function.