Significant Reduction In Serum Creatinine Research Articles

Bioenhanced advanced third generation solid dispersion of tadalafil: Repurposing with improved therapy in pyelonephritis

Tadalafil (TDL) a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN). However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD) of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC) to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDL-SMEC-SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml) in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w), exceptionally low contact angle (9°), rapid in-vitro release (t50 7.3 min), microemulsion formation (globule size ~100 nm) in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMEC-SD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.

Effect of weight loss on renal function in overweight and obese patients with heart failure

AimsThe effect of intentional weight loss on glomerular filtration rate (GFR) in overweight and obese patients with heart failure (HF), diabetes mellitus (DM) and/or metabolic syndrome (MS) has not been studied. The purpose of the present study is to assess the short term effects of intentional weight loss on renal function in this population. Materials and methodsFifty nine patients were recruited to participate in a 3-month intensive behavioral weight management intervention and received one of two standard structured energy-restricted meal plans (1200 or 1500kcal/day) based on their computed calorie deficit. Weight and renal function (serum creatinine, BUN and estimated glomerular filtration rate based on two formulas – Modification in Renal Disease Study (MDRD), and modified version of Cockcroft-Gault formula reported by Salazar Corcoran for obese patients (absolute and relative formulas) – were evaluated at baseline and at 3 months. ResultsParticipants had eGFR in the normal range at baseline and lost an average of 7.56±14.9 pounds (p<0.0001) over 3 months; however, there was no significant reduction in serum creatinine, BUN or eGFR. ConclusionThis study provides evidence that intentional weight loss in overweight and obese patients with HF along with DM, and/or MS and normal baseline renal function does not adversely affect renal function overtime.

A new combination of sitagliptin and furosemide protects against remote myocardial injury induced by renal ischemia/reperfusion in rats

Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI. In addition, the combined administration of both drugs was also investigated. Ischemia was induced in anesthetized male Wistar rats by occluding both renal pedicles for 30min followed by reperfusion for 24h. Sitagliptin (5mgkg−1), furosemide (245mgkg−1) or their combination were administered orally at 5h post-IR and 2h before euthanasia. Administration of sitagliptin or furosemide ameliorated renal and cardiac deterioration induced by renal IR. This was manifested as significant reduction of serum creatinine, urea, cystatin c, creatine kinase-MB, cardiac troponin-I and lactate dehydrogenase (P<0.05). Drug treatment significantly inhibited IR-induced elevation of TNF-α, NF-κB and caspase-3 (P<0.05) in kidney and heart tissue. In addition, they significantly suppressed malondialdehyde, NO and iNOS content, whereas they increased glutathione and antioxidative enzymes activity (P<0.05) in both tissues. Interestingly, a superior protection was observed with the combination compared to the individual drugs. We assume that this combination represents a promising regimen for managing AKI, particularly with the poor clinical outcome obtained with furosemide alone.

HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass.

Acute kidney injury (AKI) is common in patients undergoing cardiac surgery among whom it is associated with poor outcomes, prolonged hospital stays and increased mortality. Statin drugs can produce more than one effect independent of their lipid lowering effect, and may improve kidney injury through inhibition of postoperative inflammatory responses. This review aimed to look at the evidence supporting the benefits of perioperative statins for AKI prevention in hospitalised adults after surgery who require cardiac bypass. The main objectives were to 1) determine whether use of statins was associated with preventing AKI development; 2) determine whether use of statins was associated with reductions in in-hospital mortality; 3) determine whether use of statins was associated with reduced need for RRT; and 4) determine any adverse effects associated with the use of statins. We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. Randomised controlled trials (RCTs) that compared administration of statin therapy with placebo or standard clinical care in adult patients undergoing surgery requiring cardiopulmonary bypass and reporting AKI, serum creatinine (SCr) or need for renal replacement therapy (RRT) as an outcome were eligible for inclusion. All forms and dosages of statins in conjunction with any duration of pre-operative therapy were considered for inclusion in this review. All authors extracted data independently and assessments were cross-checked by a second author. Likewise, assessment of study risk of bias was initially conducted by one author and then by a second author to ensure accuracy. Disagreements were arbitrated among authors until consensus was reached. Authors from two of the included studies provided additional data surrounding post-operative SCr as well as need for RRT. Meta-analyses were used to assess the outcomes of AKI, SCr and mortality rate. Data for the outcomes of RRT and adverse effects were not pooled. Adverse effects taken into account were those reported by the authors of included studies. We included seven studies (662 participants) in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, pre-operative statin treatment was not associated with a reduction in postoperative AKI, need for RRT, or mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to -11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin group compared to placebo. Analysis of currently available data did not suggest that preoperative statin use is associated with decreased incidence of AKI in adults after surgery who required cardiac bypass. Although a significant reduction in SCr was seen postoperatively in people treated with statins, this result was driven by results from a single study, where SCr was considered as a secondary outcome. The results of the meta-analysis should be interpreted with caution; few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Large high quality RCTs are required to establish the safety and efficacy of statins to prevent AKI after cardiac surgery.

Administration of α-Galactosylceramide Improves Adenine-Induced Renal Injury.

Natural killer T (NKT) cells are a subset of lymphocytes that reacts to glycolipids presented by CD1d. Invariant NKT cells (iNKT) correspond to >90% of the total population of NKTs and reacts to α-galactosylceramide (αGalCer). αGalCer promotes a complex mixture of Th1 and Th2 cytokines, as interferon (IFN)-γ and interleukin (IL)-4. NKT cells and IFN-γ are known to participate in some models of renal diseases, but further studies are still necessary to elucidate their mechanisms. The aim of our study was to analyze the participation of iNKT cells in an experimental model of tubule-interstitial nephritis. We used 8-wk-old C57BL/6j, Jα18KO and IFN-γKO mice. They were fed a 0.25% adenine diet for 10 d. Both adenine-fed wild-type (WT) and Jα18KO mice exhibited renal dysfunction, but adenine-fed Jα18KO mice presented higher expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF)-α and type I collagen. To analyze the role of activated iNKT cells in our model, we administered αGalCer in WT mice during adenine ingestion. After αGalCer injection, we observed a significant reduction in serum creatinine, proinflammatory cytokines and renal fibrosis. However, this improvement in renal function was not observed in IFN-γKO mice after αGalCer treatment and adenine feeding, illustrating that this cytokine plays a role in our model. Our findings may suggest that IFN-γ production is one of the factors contributing to improved renal function after αGalCer administration.

Management of Postbiopsy Arteriovenous Fistulas in Transplanted Kidneys and Effectiveness of Endovascular Treatment: A Single-center Experience

We sought to evaluate the best therapeutic management of postbiopsy arteriovenous fistulas (AVFs) in transplanted kidneys. Between January 2005 and December 2011, we observed 17 cases of postbiopsy AVF in transplanted kidneys (9 asymptomatic; 8 symptomatic). Asymptomatic cases were managed conservatively, while patients with symptomatic AVF underwent endovascular treatment. We used a technique that consisted in a superselective transcatheter embolization of the afferent branch. We evaluated the technical success (postoperative closure of AVF), the immediate clinical efficacy (cessation of symptoms), and clinical efficacy at follow-up (measurement of serum creatinine at 7 days and 6 and 12 months compared with preoperative levels using t-tests). Asymptomatic AVFs resolved spontaneously, while the endovascular treatment in symptomatic AVFs showed a complete technical and clinical success with prompt remission of the presented symptoms. We observed a statistically significant reduction in serum creatinine at 7 days and 6 and 12 months postoperatively (mean creatinine--preoperative: 3.23 ± 1.4 mg/dL; 7 days: 2.25 ± 0.8 mg/dL; 6 months: 1.65 ± 0.28 mg/dL; 12 months: 1.4 ± 0.26 mg/dL; in all cases P < 0.05). In our experience, asymptomatic AVFs could be managed conservatively with close follow-up while the endovascular treatment for symptomatic AVFs is both safe and effective in the short- and long-term.

Endovascular treatment of transplanted renal artery stenosis with PTA/stenting

We evaluated the effectiveness of endovascular treatment with percutaneous transluminal balloon angioplasty (PTA)/stenting of transplanted renal artery stenosis (TRAS). Between January 2005 and December 2010, 17 patients (4 women, 13 men; mean age 60.9 years) with TRAS underwent PTA/stenting. The parameters analysed were: technical success, pre- and post-treatment serum creatinine (SCr) and blood pressure (BP), average number of antihypertensive drugs administered before and after treatment and vessel patency on colour Doppler ultrasound (CDUS) at 1, 3, 6 and 12 months and once a year thereafter. Technical success was 100%. During a mean follow-up of 28.3±18.7 months, there was a statistically significant reduction in SCr and BP values. In 18 % of cases, moderate (<60%) restenosis was observed on CDUS without renal failure and not requiring new treatment. There was a reduction in antihypertensive drugs from an average of 3.5±0.5 to 1.5±0.5. Consistent with the literature data, our experience shows that endovascular treatment with PTA/stenting is a safe and effective option for managing TRAS and can thus be considered the method of choice.

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure.

Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats. Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot. Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group. Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

Randomized comparative study of the moxonidine effectiveness in patients with uncomplicated hypertensive crisis. (AVES)

Objective. Evaluate the clinical efficacy and safety of moxonidine selective inhibitor of imidazoline I1-receptors, compared with angiotensin-converting enzyme inhibitor captopril in patients with uncomplicated hypertensive crisis (UHC). Material and Methods used in Study.The Study has been conducted on 225 patients (125 female and 100 male), average age 56.2±14.4 with uncomplicated hypertensive crisis (UHC). All patients were randomly divided into two groups: patients in moxonidine group (n=113) received a single dose of 0.4 mg moxonidine orally and patients in captopril group (n=112) received a single dose of 25 mg captopril. Along with general clinical tests, the following tests were conducted: dynamic measurement of blood pressure (BP), heart rate, electrocardiogram, creatinine, potassium and glucose levels in blood. Performance indicators for patients were the time of onset of antihypertensive effect, blood pressure level and duration of antihypertensive effect. To evaluate each medicament effectiveness, the blood pressure monitoring has been performed daily. Output dynamics were analyzed for 12 hours. Results. Anti-hypertensive effect, expressed in terms of a significant reduction in systolic blood pressure in both groups, has been reached after 30 minutes, significant reduction in diastolic blood pressure - after 60 minutes, following the administration of drugs. Level of BP reduction did not exceed 25% of the baseline. Moxonidine advantage was detected primarily in the course of anti-hypertensive action with sustained drop in blood pressure over the entire period of observation. The favorable metabolic effects of moxonidine were confirmed. In particular, its effects were manifested in significant reduction of serum creatinine. When compared, in moxonidine group 26.9% more of the patients were with efficiency above satisfactory, tolerance above satisfactory - 18.8% more than in captoril group.Conclusions. The results show a higher level of moxonidine efficacy and a good degree of tolerability in comparison with captopril in patients with uncomplicated hypertensive crises. The drug can be successfully used for treatment of uncomplicated hypertensive crises, starting in the phase prior to admission to hospital, especially in patients with concomitant illnesses (diabetes, metabolic syndrome, chronic renal failure).

Terlipressin: An Asset for Hepatologists!

Terlipressin: An Asset for Hepatologists!

Enhancing Complement Control on Endothelial Barrier Reduces Renal Post-Ischemia Dysfunction

Excessive complement activation is an integral part of ischemia and reperfusion (IR) injury (IRI) of organs. In kidney transplantation, the pathologic consequence of IRI and complement activation can lead to delayed graft function, which in turn is associated with acute rejection. Previous strategies to reduce complement-induced IRI required systemic administration of agents, which can lead to increased susceptibility to infections/immune diseases. The objective of this study was to determine whether an increase in complement control defenses of rat kidney endothelium reduces IRI. We hypothesized that increased complement control on the endothelial barrier reduces IR-mediated complement activation and reduces kidney dysfunction. Fischer 344 rats underwent left kidney ischemia for 45 min and treatment with a novel fusogenic lipid vesicle (FLVs) delivery system to decorate endothelial cells with vaccinia virus complement control protein (VCP), followed by reperfusion for 24 h. Assessment included renal function by serum creatinine and urea, myeloperoxidase assay for neutrophil infiltration, histopathology, and quantification of C3 production in kidneys. Animals in which the kidney endothelium was bolstered by FLVs+VCP treatment had better renal function with a significant reduction in serum creatinine compared with vehicle controls (P < 0.05). Also, C3 production was significantly reduced (P < 0.05) in treated animals compared with vehicle controls. Increasing complement control at the endothelial barrier with FLVs+VCP modulates complement activation/production during the first 24 h, reducing renal dysfunction following IRI.

Effect of Bardoxolone Methyl on Kidney Function in Patients with T2D and Stage 3b–4 CKD

Background/Aims: Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules. Methods: This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days. Results: The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m² (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (–0.3 mg/dl) and blood urea nitrogen (–4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m²), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported. Conclusions: The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function.

Enhancing complement control on endothelial barrier reduces renal dysfunction following ischemia/reperfusion injury

Excessive complement activation following ischemia and reperfusion (IR) of organs disrupts endothelial barrier, mediates inflammation and subsequent tissue injury. Previous strategies to reduce complement induced IR injury required systemic administration of agents, which can lead to increased susceptibility to infections/immune diseases. The objective of this project was to determine whether an increase in complement control defenses of rat kidney endothelium reduces IR injury. We hypothesized that increased complement control on the endothelial barrier reduces IR‐mediated complement activation and reduces kidney dysfunction. Fisher rats underwent left kidney ischemia for 45 min. and treatment with a novel fusogenic lipid vesicle (FLVs) delivery system to decorate endothelial cells with an anti‐complement protein, His6‐VCP followed by reperfusion for 24h. Assessment included renal function by serum creatinine and urea, myeloperoxidase assay for neutrophil infiltration, histopathology and immunohistochemistry. Animals in which the kidney endothelium was bolstered by His6‐VCP had better renal function with a significant reduction in serum creatinine as compared to controls (lactated ringer's only). Neutrophil infiltration showed a downward trend. We conclude that FLVs/His6‐VCP therapy was effective during the first 24h in reducing vascular and renal dysfunction following IR injury.

Administration of Neural Precursor Cells Ameliorates Renal Ischemia-Reperfusion Injury

In this study we evaluated whether administration of stem cells of neural origin (neural precursor cells, NPCs) could be protective against renal ischemia-reperfusion injury (IRI). We hypothesized that stem cell outcomes are not tissue-specific and that NPCs can improve tissue damage through paracrine mechanisms, especially due to immunomodulation. To this end, Wistar rats (200–250 g) were submitted to 1-hour ischemia and treated with NPCs (4 × 10⁶ cells/animal) at 4 h of reperfusion. To serve as controls, ischemic animals were treated with cerebellum homogenate harvested from adult rat brain. All groups were sacrificed at 24 h of reperfusion. NPCs were isolated from rat fetus telencephalon and cultured until neurosphere formation (7 days). Before administration, NPCs were labeled with carboxyfluorescein diacetate succinimydylester (CFSE). Kidneys were harvested for analysis of cytokine profile and macrophage infiltration. At 24 h, NPC treatment resulted in a significant reduction in serum creatinine (IRI + NPC 1.21 + 0.18 vs. IRI 3.33 + 0.14 and IRI + cerebellum 2.95 + 0.78mg/dl, p < 0.05) and acute tubular necrosis (IRI + NPC 46.0 + 2.4% vs. IRI 79.7 + 14.2%, p < 0.05). NPC-CFSE and glial fibrillary acidic protein (GFAP)-positive cells (astrocyte marker) were found exclusively in renal parenchyma, which also presented GFAP and SOX-2 (an embryonic neural stem cell marker) mRNA expression. NPC treatment resulted in lower renal proinflammatory IL1-β and TNF-α expression and higher anti-inflammatory IL-4 and IL-10 transcription. NPC-treated animals also had less macrophage infiltration and decreased serum proinflammatory cytokines (IL-1β, TNF-α and INF-γ). Our data suggested that NPC therapy improved renal function by influencing immunological responses.

The Effects of Rapamycin in the Progression of Renal Fibrosis

Renal fibrosis is a hallmark of end-stage renal diseases and of chronic allograft nephropathy (CAN). Rapamycin, besides its action through blockade of lymphocyte proliferation, also has antiproliferative, antiviral, and antitumor actions. Its use in clinical in patients with CAN has recently been advocated. Objectives Our goal was to evaluate the effect of rapamycin in an established model of renal fibrosis, unilateral ureteral obstruction. Materials and Methods C57BL/6 mice were divided into two groups, treated or not with daily doses of rapamycin (0.2 mg/kg) beginning on day-1. The obstruction was performed as day 0. Blood and kidney tissues were collected at 1, 4, 7, and 14 days after the surgery to quantify bone morphogenic protein (BMP)-7 and transforming growth factor (TGF)-β mRNA by real time PCR. Results Daily treatment with rapamycin caused a significant reduction in serum creatinine at day 1 (0.57 ± 0.03 vs 0.95 ± 0.15 mg/dL, P = .002) and at day 14 (0.56 ± 0.04 vs 0.73 ± 0.07 mg/dL, P = .040). This profile was corroborated by histological morphometric analyses showing less fibrosis at day 14. However, rapamycin surprisingly induced an upregulation of TGF-β at day 4 (3.05 ± 0.46 vs 1.85 ± 0.41, P = .006) and at day 7 (6.33 ± 0.55 vs 4.97 ± 0.38, P = .024) with a reduced expression by day 14 (4.03 ± 1.07 vs 7.89 ± 0.83, P < .001). Surprisingly, rapamycin also promoted an increment in BMP-7, completely reversing the ratio of TGF-β to BMP-7, allowing a more protective phenotype. Conclusion Rapamycin slightly ameliorated the renal dysfunction and, at later time points, induced less fibrosis and less decrease in the TGF-β to BMP-7 ratio.

The nephrologist in the HAART era

The nephrologist in the HAART era

Erythropoietin improves anemia exercise tolerance and renal function and reduces B-type natriuretic peptide and hospitalization in patients with heart failure and anemia

Anemia is now recognized as being a common finding in CHF and is associated with increased mortality and morbidity. However, it is uncertain whether the anemia is actually causing the worse prognosis or is merely a marker of more severe cardiac disease. Previous intervention studies with subcutaneous (s.c.) beta-EPO in combination with iron have either been uncontrolled or case-controlled studies. We report a randomized, double-blind, placebo-controlled study of the combination of s.c. EPO and oral iron versus oral iron alone in patients with anemia and resistant CHF. The present study examines, in patients with advanced congestive heart failure (CHF) and anemia, the effects of beta-erythropoietin (EPO) and oral iron on the anemia and on cardiac and renal functional parameters. Forty consecutive subjects with moderate to severe CHF and anemia (hemoglobin [Hb] <11 g/dL) were studied. They were randomized to receive, in a double-blind fashion, either (a) (group A, the treatment group, 20 patients) s.c. beta-EPO for 3 months twice weekly, in addition to daily oral iron, or (b) (group B, the placebo group, 20 patients) normal saline in s.c. injections and daily oral iron. Two patients in group B were eventually excluded because of a fall of Hb <8 g/dL requiring transfusion, leaving 18 patients in group B. After the 3-months study, the group A patients were maintained on the same treatment for an additional 9 months, whereas in Group B, the placebo and oral iron were stopped. In group A, after a mean of 3.5 +/- 0.8 months of treatment, there was a significant increase in Hb from 10.4 +/- 0.6 to 12.4 +/- 0.8 g/dL (P < .01); a significant improvement in New York Heart Association functional class from 3.5 +/- 0.6 to 2.8 +/- 0.5 (P < .05); a longer endurance time on exercise testing, from 5.8 +/- 2.2 to 7.8 +/- 2.5 minutes (P < .01); a greater distance walked on exercise testing, from 278 +/- 55 to 356 +/- 88 meters (P < .01); a significant increase in the peak oxygen consumption (VO2) from 12.8 +/- 2.8 to 15.1 +/- 2.8 mL/kg per minute (<.05); and the VO2 at the anaerobic threshold, from 9.2 +/- 2.0 to 13.2 +/- 3.6 mL/kg minute (P < .01). There was also a significant fall in plasma B-type natriuretic peptide levels from 568 +/- 320 to 271 +/- 120 pg/mL (P < .01), a significant reduction in serum creatinine (P < .01), and an increase in estimated creatinine clearance (P < .05). In group B, there were no significant changes in any of the above parameters over the study period. At the end of the 1-year study, the Hb was still higher in group A than group B, and the rate of hospital admissions/patients over the year averaged 0.8 +/- 0.2 in group A and 1.7 +/- 0.8 in group B (P < .01). In anemic CHF patients, correction of anemia with EPO and oral iron leads to improvement in New York Heart Association status, measured exercise endurance, oxygen use during exercise, renal function and plasma B-type natriuretic peptide levels and reduces the need for hospitalization.

A randomised, double blind, placebo controlled trial of the effect of theophylline in prevention of vasomotor nephropathy in very preterm neonates with respiratory distress syndrome

Background: Vasomotor nephropathy is a common renal dysfunction in very preterm neonates. Objective: To determine whether theophylline could prevent vasomotor nephropathy in very preterm infants with respiratory distress syndrome. Methods:...

Effects of STZ-induced diabetes and its treatment with vanadyl sulphate on cyclosporine A-induced nephrotoxicity in rats

The aim of this study was to analyze the effect of streptozotocin (STZ)-induced diabetic state and the insulin-like acting, vanadyl sulphate (VS) on cyclosporine A (CyA) related nephrotoxicity in rats. Male Wistar rats were divided into six groups, of 12 animals each: The control, diabetic rats and diabetic rats whose drinking VS in the drinking water in a concentration of 1 mg/ml. Another three similarly treated groups were injected intra-peritoneally (ip) with CyA in a dose of 25 mg/kg/day for ten doses, 10 days after diabetic induction by using a single dose of STZ of 65 mg/kg. Rats were sacrificed 48 h after the last CyA dose and serum as well as kidneys were isolated and analyzed. Treatment with CyA to control normoglycemic rats resulted in significant increases in kidney weight, serum creatinine, urea nitrogen, cholesterol and triglycerides (TG) levels. Also, the kidney tissue of CyA-treated control animals showed significant increases in total nitrate/nitrite (NO(x)) concentration and malondialdehyde (MDA) production level as well as depletion of glutathione (GSH) content and glutathione peroxidase (GSH-P(x)) activity level. Histopathologic evaluation of CyA-treated control rats revealed tubular atrophy, hyaline casts and focal tubular necrosis. However, treatment of diabetic rats with CyA showed significant reduction in serum creatinine and elevation in TG level as well as reductions in the kidney NO(x) concentration and MDA production level and increase in GSH concentration compared to CyA-treated control rats. Moreover, histopathology of the kidney of CyA-treated diabetics showed typical changes of the diabetic controls revealing glomerular hypertrophy and tubular dilation. On the other hand, treatment with CyA to those diabetic animals administered VS in the drinking water resulted in exacerbation of renal dysfunction, manifested by significant increases in serum indices of nephrotoxicity, cholesterol, TG and bilirubin levels. Also, VS administration to CyA-treated diabetics showed significant increase in kidney NO(x) concentration compared to those CyA-treated diabetics drinking plain tap water, and to a level significantly lower than those CyA-treated controls. Histopathologically, kidney of CyA/VS-treated diabetic showed marked CyA related changes. In conclusion, STZ-induced diabetes might provide partial protection against CyA-induced renal dysfunction. Also, treatment of hyperglycemia with VS might exacerbate CyA related nephrotoxicity.

Haemodialysis for the prevention of contrast-induced nephropathy: outcome of 31 patients with severely impaired renal function, comparison with patients at similar risk and review.

To investigate whether haemodialysis prevents contrast-induced nephropathy (definition: increase of serum-creatinine of >or= 0.5 mg/dL within 7 days). Thirty-one patients (mean serum-creatinine 4.01 +/- 1.83 mg/dL) were dialyzed for 4.36 +/- 1.0 hours within one hour after 278.4 +/- 160.5 mL of contrast medium. Dialysis resulted in a significant reduction of serum-creatinine (2.25 +/- 1.46 mg/dL; P< 0.0001) and stable mean serum-creatinine levels 2, 3, 4, and 7 days after contrast medium and at discharge compared with baseline values. However, 19 patients (61%) developed contrast-induced nephropathy within 7 days. Four patients had to be repeatedly dialyzed. A comparison of our patients' 48 hours-incidence of contrast-induced nephropathy (9/31; 29%) versus patients at comparable risk included in seven previous studies demonstrated a prophylactic effect of dialysis only versus a subgroup in one study. Data provide no hint that haemodialysis prevents contrast-induced nephropathy. Therefore, postprocedural dialysis should be restricted to patients participating in clinical studies.