Elevated Serum Levels Of Creatinine Research Articles

Nebivolol ameliorates sepsis-evoked kidney dysfunction by targeting oxidative stress and TGF-β/Smad/p53 pathway

Sepsis is a potential fetal organ destruction brought on through an overzealous immunologic reaction to infection, causing severe inflammation, septic shock, and damage to different organs. Although there has been progress in the identification and controlling of clinical sepsis, the fatality rates are still significant. This study, for the first time, intended to examine the possible ameliorative impact of Nebivolol, a β1-adrenergic antagonist antihypertensive drug, against nephrotoxicity resulted from cecal ligation and puncture (CLP)-induced sepsis in rats, on molecular basis. Sixty male Wistar albino rats were chosen. Oxidative stress indicators and biochemical markers of kidney activity were evaluated. Inflammatory mediators, fibrosis- and apoptosis-related proteins and gene expressions were investigated. Moreover, renal histopathological investigation was performed. CLP-induced nephrotoxicity characterized by markedly elevated serum levels of creatinine, blood urea nitrogen, uric acid, and renal malondialdhyde. On the other hand, it decreased serum total protein level, renal superoxide dismutase activity and reduced glutathione level. Additionally, it significantly elevated the renal inflammatory mediators (tumor necrosis factor-alpha, ilnerlukin (IL)-6, and IL-1β) and Caspase-3 protein, reduced IL-10 level, amplified the expression of transforming growth factor-beta 1 (TGF-β1), p-Smad2/3 and alpha-smooth-muscle actin proteins, downregulated the B cell lymphoma-2 (Bcl-2) gene and elevated the transcription of Bcl-2-associated X-protein (Bax), p53 and Nuclear factor-kappa B (NF-κB) genes. Furtheremor, kidney tissues exhibited significant histopathological changes with CLP. On the contrary, Nebivolol significantly improved all these biochemical changes and enhanced the histopathological alterations obtained by CLP. This research showed, for the first time, that Nebivolol effectively mitigated the CLP-induced kidney dysfunction via its antioxidant, antifibrotic and anti-apoptotic activity through modulation of oxidative stress, TGF-β/NF-κB and TGF-β/Smad/p53 signaling pathways.

Amlodipine alleviates renal ischemia/reperfusion injury in rats through Nrf2/Sestrin2/PGC-1α/TFAM Pathway

BackgroundPreviously, observational studies showed that amlodipine can mitigate calcineurin inhibitor- and contrast-induced acute kidney injury (AKI). Herein, we aimed to measure the effect of amlodipine on renal ischemia/reperfusion (I/R) injury and find the underlying mechanisms.Materials and methodsBilateral renal I/R was induced by clamping the hilum of both kidneys for 30 min. The first dose of amlodipine 10 mg/kg was gavaged before anesthesia. The second dose of amlodipine was administered 24 h after the first dose. Forty-eight hours after I/R, rats were anesthetized, and their blood and tissue specimens were collected.ResultsAmlodipine significantly decreased the elevated serum levels of creatinine and blood urea nitrogen (BUN) and mitigated tissue damage in hematoxylin & eosin (H&E) staining. Amlodipine strongly reduced the tissue levels of malondialdehyde (MDA), interleukin 1β (IL1β), and tumor necrosis factor α (TNF-α). Amlodipine enhanced antioxidant defense by upregulating nuclear factor erythroid 2-related factor 2 (Nrf2) and Sestrin2. Furthermore, amlodipine significantly improved mitochondrial biogenesis by promoting Sestrin2/peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α)/mitochondrial transcription factor A (TFAM) pathway. It also enhanced autophagy and attenuated apoptosis, evidenced by increased LC3-II/LC3-I and bcl2/bax ratios after renal I/R.ConclusionThese findings suggest that amlodipine protects against renal I/R through Nrf2/Sestrin2/PGC-1α/TFAM Pathway.

Hippocratea africana root extract and fractions attenuate paracetamol-induced oxidative stress and kidney injuries in rats

Hippocratea africana root used locally in the treatment of poisoning was investigated to confirm its antidotal potential in rats. The root extract (200-600 mg/kg) and fractions; dichloromethane (DCM) and aqueous, 400 mg/kg) were evaluated for nephroprotective activity against paracetamol-induced kidney injury in rats. Anti-oxidative stress and renoprotective potentials of root extract and fractions were assessed by determining oxidative stress markers levels, kidney function parameters and histopathology in rats. The root extract and fractions caused significant (p<0.05 – 0.001) increases in the levels of oxidative stress markers (SOD, CAT, GPx, GSH) in the kidney, while MDA level was decreased. The root extract/fractions caused significant (p<0.05-0.001) reduction of elevated serum levels of creatinine and urea of the rats, while the electrolytes levels were considerably reduced though not significant. Histology of kidney revealed absence or significant reductions in pathological features in the treated rats compared to paracetamol treated group group. The results show that the root extract and fractions of H.africana have antioxidative stress and nephroprotective potentials which may be due to the antioxidant activities of their phytochemical constituents.

Rutin and Hesperidin Alleviate Paclitaxel-Induced Nephrocardiotoxicity in Wistar Rats via Suppressing the Oxidative Stress and Enhancing the Antioxidant Defense Mechanisms.

Paclitaxel is a primary chemotherapy agent that displays antitumor activity against a variety of solid tumors. However, the clinical effectiveness of the drug is hampered by its nephrotoxic and cardiotoxic side effects. Thus, this investigation aimed at assessing the protective effects of rutin, hesperidin, and their combination to alleviate nephrotoxicity caused by paclitaxel (Taxol), cardiotoxicity in male Wistar rats, as well as oxidative stress. Rutin (10 mg/kg body weight), hesperidin (10 mg/kg body weight), and their mixture were given orally every other day for six weeks. Rats received intraperitoneal injections of paclitaxel twice weekly, on the second and fifth days of the week, at a dose of 2 mg/kg body weight. In paclitaxel-treated rats, the treatment of rutin and hesperidin decreased the elevated serum levels of creatinine, urea, and uric acid, indicating a recovery of kidney functions. The cardiac dysfunction in paclitaxel-treated rats that got rutin and hesperidin treatment also diminished, as shown by a substantial reduction in elevated CK-MB and LDH activity. Following paclitaxel administration, the severity of the kidney and the heart's histopathological findings and lesion scores were markedly decreased by rutin and hesperidin administration. Moreover, these treatments significantly reduced renal and cardiac lipid peroxidation while markedly increased GSH content and SOD and GPx activities. Thus, paclitaxel likely induces toxicity in the kidney and the heart by producing oxidative stress. The treatments likely countered renal and cardiac dysfunction and histopathological changes by suppressing oxidative stress and augmenting the antioxidant defenses. Rutin and hesperidin combination was most efficacious in rescuing renal and cardiac function as well as histological integrity in paclitaxel-administered rats.

Mortality and prognostic factors in hospitalized COVID-19 patients with cancer: an analysis from a large healthcare system in the United States.

To evaluate clinical outcomes in patients with malignancy who are SARS-CoV-2 (COVID-19) positive and investigate if factors such as age, gender, and race contribute to COVID-19 mortality in patients with malignancy. Retrospective data was gathered from Memorial Healthcare System of COVID-19 patients hospitalized from March 1, 2020 to January 18, 2021. Active malignancy was defined as either receiving antineoplastic therapy or being under surveillance. The primary endpoint was in-hospital mortality. Descriptive statistics were used to summarize the characteristics and outcomes. Univariate and multivariate logistic analysis were performed to define baseline clinical characteristics potentially associated with mortality in cancer patients with COVID-19. A total of 4,870 COVID-19 patients were enrolled in the study, and 265 of those patients had a diagnosis of active malignancy. The study population was diverse which included non-Hispanic whites (NHW) 816 (16.8%), Hispanics 2,271 (46.6%) and Blacks 1,534 (31.5%). Of the cancer patients, 24.1% were NHW, 43% were Hispanic and 28.7% were Black. Amongst the races, 37.5% of in-hospital mortalities were NHW, while 18.4% were Hispanics and 19.7% were Black. The in-hospital mortalities amongst the two malignancy types, solid and hematological, accounted for 24.6% and 23.5% of deaths and they were not found to be statistically significant (P=0.845). After adjustments for age, gender and race were made, cancer was independently associated with an increased in-hospital mortality, with an adjusted odds ratio of 1.48 [95% confidence interval (CI): 1.08-2.01]. Increased age and elevated serum levels of creatinine and C-reactive protein (CRP) were associated with an increased risk of death in cancer patients with COVID-19. COVID-19 in patients with cancer had poorer outcomes in comparison to those who were cancer-free. Both hematological and solid malignancies had similar in-hospital mortality rates. The highest in-hospital mortalities of cancer patients with COVID-19 were non-Hispanic whites in-comparison to Hispanics with the least. Age, elevated levels of creatinine and CRP were independently associated with increased risk of death in cancer patients hospitalized with COVID-19. The findings indicate the need for close surveillance and monitoring of these patients as they are more likely to have higher risk of death from COVID-19.

Studies on Nephroprotective Effect of Methanolic and Aqueous Extract of Bark of Pithecellobium Dulce Roxb. in Rats

Kidney failure is a major problem of worldwide proportions. Kidney injury is a sudden loss of kidney function resulting in the accretion of waste materials such as creatinine and urea in the body. There are various agents that exert nephrotoxic effects through distinctive morbific defence mechanisms. Gentamicin, cisplatin and paracetamol are among common nephrotoxicity agents. In recent years, natural compounds are being expanded used in the treatment of kidney diseases. With this backdrop the study has been designed with the aim to studies on nephroprotective effect of methanolic and aqueous extract of bark of Pithecellobium Dulce Roxb. in rats. The methanolic and aqueous extracts of bark of P. Dulce was studied for nephroprotective effect in female Wistar rats against cisplatin, gentamicin and paracetamol induced nephrotoxicity, by estimating serum creatinine, blood urea and serum albumin levels. The dried bark of P. Dulce, Roxb (Leguminosae), contains tannins, flavonoids, triterpenoids, beta-sitosterol and saponin glycoside. Treatments with the methanolic and aqueous extracts could significantly (P is less than 0.001) reduce the elevated serum levels of creatinine, blood urea and serum albumin. P. Dulce bark extracts significantly prevented the physical, biochemical, histological and structural changes induced by cisplatin, gentamicin and paracetamol in the kidney. The present study reports with the exploration of P. Dulce bark extracts possessed implicit nephroprotective activity. This activity may be attributed due to the abundant phytoconstituents of the plant extracts.

Efficacy of tenofovir disoproxil fumarate switch therapy in chronic hepatitis B patients with suboptimal response to adefovir‑based combination therapy

In the present study, the efficacy and safety of tenofovir disoproxil fumarate (TDF) switch therapy were assessed in patients with chronic hepatitis B exhibiting a suboptimal response to adefovir (ADV)-based combination therapy. First, the efficacy of the TDF switch therapy was retrospectively evaluated in 50 patients with chronic hepatitis B who failed to respond to ADV-based combination treatment. Among those, 48 patients with a median age of 35 years were hepatitis B e antigen (HBeAg)-positive and 17, 14 and 19 patients were previously treated with lamivudine (LAM) plus ADV, telbivudine plus ADV and entecavir (ETV) plus ADV, respectively. A total of 41 patients were treated with TDF alone and 9 with TDF plus ETV. The median time of follow-up was 102 weeks. The primary end-point was the cumulative probability of achieving a complete virologic response (CVR). The secondary end-points were the rate of alanine aminotransferase (ALT) normalization, HBeAg seroconversion in HBeAg-positive patients, and the plasma levels of creatinine and creatine kinase. The mean serum hepatitis B virus DNA levels prior to initiation of the TDF switch therapy were 4.8±1.6 log10IU/ml. The cumulative probability of achieving a VR at 24, 48, 96 and 108 weeks was 52.0, 76.0, 89.8 and 94.9%, respectively. The cumulative probability of normalization of ALT at 12, 24, 36, 48, 60,72, 84, 96, 108, 120 and 132 weeks was 34, 44, 50, 58, 66, 70, 74, 80, 90, 92 and 94%, respectively. HBeAg seroconversion was achieved in 5 patients. During the follow-up, 6 patients suffered from a virologic breakthrough, 3 patients failed to respond to the TDF treatment and the remaining patients were able to obtain VR following the continuation of TDF treatment. Slightly elevated serum levels of creatinine were observed in one patient, whereas creatine kinase activity did not increase in any of the subjects. In conclusion, TDF switch therapy is efficient and safe for patients with chronic hepatitis B with a suboptimal response to ADV-based combination therapy.

Hydroxychloroquine sulphate therapy of erosive oral lichen planus.

Erosive oral lichen planus (LP) may be painful and debilitating. Symptomatic oral LP has been treated with a wide spectrum of topical and systemic therapies, but few have been evaluated in large series. Hydroxychloroquine is suggested to be effective in oral LP. Twenty-one consecutive patients with erosive, biopsy-confirmed oral LP were prescribed. hydroxychloroquine sulphate 400 mg/day. Symptomatic improvement was evaluated by means of a visual analogue scale into three groups: no change, moderate to marked improvement and complete remission. Five (24%) patients obtained complete remission, 12 (57%) patients showed moderate to marked improvement, 3 (14%) patients did not improve at all and in one patient therapy was terminated after 1 month due to side effects. Response to therapy was observed after 2-4 months. Side effects which ultimately led to termination of therapy in three patients were elevated creatinine serum levels (after 1 month), visual field defects (after 8 months) and hyperpigmentation (after 24 months). Among six patients who responded to therapy, three flared on stopping. Hydroxychloroquine sulphate may be effective and relatively safe treatment for erosive oral LP.

Nephroprotective effect of electrolyzed reduced water against cisplatin-induced kidney toxicity and oxidative damage in mice

BackgroundCisplatin is a potent chemotherapeutic drug for cancer therapy, but it has serious side effects in clinical treatment, particularly nephrotoxicity. The purpose of this study was to evaluate the protective effect of electrolyzed reduced water (ERW) on renal injury caused by cisplatin. MethodsAnimals were divided into four groups as follows: normal control group, cisplatin control group, ERW control group and ERW + cisplatin group. Each group comprised 10 animals, which were orally treated with normal saline or ERW daily companion by administration of one dose of cisplatin for 28 days. Animals in the cisplatin group received an intraperitoneal single-dose injection of cisplatin (20 mg/kg body weight) as a single i.p. dose on the 25th day of the experiment. We determined the hydration state in urine and the level of serum markers of kidney function, the levels of glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) levels and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxidase dismutase (SOD) in kidney and histopathological changes. ResultsAfter administration of ERW, the reduced urinary osmolality was increased and elevated Na+, K+, Mg2+ and Ca2+ levels in urine were significantly decreased in cisplatin-induced renal injury mice. Besides, the results demonstrated that significantly decreased elevated serum levels of creatinine and blood urea nitrogen (BUN) and the levels of TBARS in the kidneys that were induced by cisplatin. Moreover, ERW treatment was also found to markedly increase (p < 0.05) the activities of GPx, GR, CAT and SOD, and to increase GSH content in the kidneys. Histopathology showed that ERW protects against cisplatin-induced renal injury to both the proximal and distal tubules. ConclusionERW exhibits potent nephroprotective effects on cisplatin-induced kidney damage in mice, likely due to both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.

The metabolic profile of a rat model of chronic kidney disease.

BackgroundThe kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension.MethodsWe used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney.ResultsDS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased.ConclusionsDS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

Possible Protective Effect of Natural Extracts of Rosemary and Parsley Against Isoniazid-induced Nephrotoxicity in Adult Male Albino Rats

The treatment of tuberculosis (TB) has been reported to induce nephrotoxicity arised in association with hepatotoxicity. Isoniazid (INH), being the first line drug used as anti-tuberculosis drugs, is known to induce renal toxicity associated with hepatotoxicity leading to termination of therapy in patients during the intensive phase. The present study aims to determine the protective effect of rosemary (Rosmarinus officinalis) and parsley (Petroselinum crispum) aqueous extracts against Isoniazid-induced nephrotoxicity. To achieve this purpose, two main experiments were conducted; short-term study for 4 weeks and long-term one for 8 weeks. Adult male albino rats (120-150g) were randomly divided into 6 groups for each experiment (10 animals each) as follows: group (1) rats administrated with saline and served as control, group (2) animals orally administrated with rosemary extract (440mg/kg body weight./day), group (3) animals administrated with parsley extract (250 mg/kg body weight./day), group (4) rats received Isoniazid alone (50 mg/kg body weight./day), group (5) rats daily received Isoniazid in combination with rosemary extract, and group (6) rats daily received Isoniazid in combination with parsley extract. The administration of natural extracts or Isoniazid was orally and daily for four weeks for the short-term experiment and for eight weeks for the long-term one. At the end of each experiment, all rats were weighed then sacrificed and the biochemical investigations indicative of kidney function as serum creatinine, urea and uric acid were assayed. In addition, serum gamma glutamy ltransferase (GGT) activity and the levels of serum inorganic ions (Na+, K+ and total Ca++) were determined. Also, the change in the body weight gain was recorded. The results revealed that administration of rosemary or parsley extract in combination with isoniazid ameliorated the Isoniazid-induced nephrotoxicity. This was evidenced by the marked improvement in kidney function as monitored through the significant decrement in the elevated serum levels of creatinine, urea and uric acid in addition to the remarkable amelioration of GGT activity. Also, the administration of parsley or rosemary extracts in combination with Isoniazid normalized to some extent, the body weight gain and the other biochemical parameters in rats compared with those intoxicated with Isoniazid only. The improvement observed in the biochemical parameters was more pronounced in long-term study compared to the short-term one. In conclusion, either rosemary or parsley extract could play an evidenced beneficial role for prevention of Isoniazid-induced nephrotoxic effects. This protective effect could be attributed to the antioxidant activity of their major constituents.

TRPV1 Ablation Aggravates Inflammatory Responses and Organ Damage during Endotoxic Shock

To test the hypothesis that ablation of transient receptor potential vanilloid type 1 (TRPV1) channels leads to exacerbated inflammatory responses and organ damage during endotoxic shock, lipopolysaccharide (LPS; 5 million endotoxin units/kg of body weight) was injected intraperitoneally (i.p.) into wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice. Mean arterial pressure and heart rate, determined by radiotelemetry, were severely depressed after LPS injection into WT and TRPV1(-/-) mice, with no distinction between the two strains. At 24 h after LPS injection, renal glomerular hypercellularity and hepatocellular injury were observed in both strains, accompanying further elevated serum levels of creatinine and alanine aminotransferase in TRPV1(-/-) mice compared to those in WT mice. At 6 or 24 h after LPS injection, neutrophil recruitment into kidneys and livers, serum cytokine (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], IL-6) and renal chemokine (KC, macrophage inflammatory protein 2 [MIP-2]) levels, and renal VCAM-1 and ICAM-1 expression were greater in TRPV1(-/-) mice than WT mice. In addition, increased plasma calcitonin gene-related peptide (CGRP) levels observed in WT mice 6 h after LPS injection were absent in TRPV1(-/-) mice. Thus, TRPV1 ablation aggravates inflammatory responses, including neutrophil infiltration, proinflammatory cytokine production, and adhesion molecule expression, leading to intensified organ damage during endotoxic shock in the absence of worsened circulatory failure. The data indicate that TRPV1 activation may attenuate endotoxin-induced organ damage, possibly via its anti-inflammatory action rather than alteration of hemodynamics.

Liposomal amphotericin B does not induce nephrotoxicity or renal function impairment in premature neonates

Liposomal amphotericin B (LAMB) is frequently administered in NICU to preterm infants <1500 g at birth (VLBW) for treatment of systemic fungal infections (SFI). Concerns exist on safety and tolerability of such drug in patients who are at risk for renal function impairment due to their prematurity. To assess the occurrence of renal function impairment related to LAMB in a 10-year cohort of VLBW neonates treated with this drug. Through database search of clinical charts, all VLBW neonates admitted to a 3(rd) level NICU in the years 1998-2007 and undergoing treatment with LAMB were identified. The occurrence of LAMB-attributable renal toxicity was investigated; infants withdrawn from treatment for development of adverse effects or toxicity were identified. In the study period, 71 of 792 admitted VLBW neonates (8.9%) underwent antifungal treatment with LAMB administered at the recommended dosages (3-to-5 mg/kg/day). Mean duration of treatment was 14 (±9) days, mean cumulative dose given was 58 (±25) mg/kg per infant. Renal compromise, defined as hypokalaemia, and/or elevated creatinine serum levels, and/or decreased urine output, occurred in 2 of 71 (2.8%) treated patients, by 5 (±3) mean days after treatment initiation. In both patients LAMB was withdrawn; renal function impairment was only mild and transient, and normal renal function was restored at discharge. No other significant adverse effects were recorded in any treated neonate. LAMB is generally safe and well tolerated in VLBW neonates. The occurrence of LAMB-related nephrotoxicity appears to be uncommon, mild and transient.

NMR‐based metabonomic approach on the toxicological effects of a Cimicifuga triterpenoid

Cimicifugae Rhizoma, a well-known botanical dietary supplement, has been the subject of intense interest due to its potential application for alleviating menopausal symptom. Although there are clinic data that the Cimicifuga extract should have hepatotoxicity, no evidence on the main chemical components has been reported. Cimicidol-3-O-β -d-xyloside (CX) is one of the main triterpenoids of the rhizome. This work studies the toxicological effects of CX after oral administration (50 mg kg(-1) per day) over a 7-day period in female SD rats using metabonomic analyses of (1) H NMR spectra of urine, serum and liver tissue extracts. Histopathological studies of liver and analyses of blood biochemical parameter, such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine revealed that CX had no negative impacts on liver and kidney. However, the metabolic signature of (1) H NMR-based urinalysis of daily samples displayed an increment in the levels of taurine, trimethylamine-N-oxide (TMAO), betaine and acetate. Elevated serum levels of creatinine, glucose, alanine, TMAO and betaine and lower levels of lactate were observed. Metabolic profiling on aqueous soluble extracts of liver showed simultaneously increases in succinate, glycogen, choline, glycerophosphorylcholine, TMAO and betaine levels and reduction in valine, glucose and lactate levels. Nevertheless, no changes in any metabonomic level were found in lipid-soluble extracts of liver. These findings indicate that CX has a slight toxicity in liver and kidney via disturbance of the metabolisms of energy and amino acids. The present study provides a reasonable explanation for the clinical hepatotoxicity of Cimicifuga extract.

Successful use of kidneys from deceased donors with acute renal failure

Kidneys from deceased donors with acute renal failure are not widely used.To compare outcomes for recipients of kidneys from donors with acute renal failure at organ recovery with outcomes for recipients of kidneys from donors with normal serum levels of creatinine.Records of deceased donors and recipients of their organs at the Saudi Center for Organ Transplantation from 2003 to 2005 were reviewed. A total of 33 donors (donating 65 kidneys to 65 recipients) with elevated serum levels of creatinine (>1.7 mg/dL) and 94 donors (donating 188 kidneys to 188 recipients) with normal (<1.1 mg/dL) serum levels of creatinine at organ recovery and their respective recipients were compared. Both groups had normal creatinine levels at admission.Recipients in both groups had similar renal function at discharge and follow-up. Delayed graft function occurred more often (P= .009) in the recipients of kidneys from donors with acute renal failure (47.7%) than in recipients of kidneys from donors with normal creatinine levels (29.8%). Elevation of serum level of creatinine at organ recovery did not correlate significantly with kidney function at discharge or last follow-up or with graft survival.Survival of patients or grafts at 1, 2, and 3 years did not differ significantly between the recipients in the 2 groups. Only the frequency of delayed graft function differed between the 2 groups.

Successful Use of Kidneys from Deceased Donors with Acute Renal Failure

Kidneys from deceased donors with acute renal failure are not widely used. To compare outcomes for recipients of kidneys from donors with acute renal failure at organ recovery with outcomes for recipients of kidneys from donors with normal serum levels of creatinine. Records of deceased donors and recipients of their organs at the Saudi Center for Organ Transplantation from 2003 to 2005 were reviewed. A total of 33 donors (donating 65 kidneys to 65 recipients) with elevated serum levels of creatinine (>1.7 mg/dL) and 94 donors (donating 188 kidneys to 188 recipients) with normal (<1.1 mg/dL) serum levels of creatinine at organ recovery and their respective recipients were compared. Both groups had normal creatinine levels at admission. Recipients in both groups had similar renal function at discharge and follow-up. Delayed graft function occurred more often (P= .009) in the recipients of kidneys from donors with acute renal failure (47.7%) than in recipients of kidneys from donors with normal creatinine levels (29.8%). Elevation of serum level of creatinine at organ recovery did not correlate significantly with kidney function at discharge or last follow-up or with graft survival. Survival of patients or grafts at 1, 2, and 3 years did not differ significantly between the recipients in the 2 groups. Only the frequency of delayed graft function differed between the 2 groups.

Renal insufficiency in patients with Crohn's disease

Background and Aim: Patients with Crohn's Disease (CD) may develop renal insufficiency. The aim of this study was to analyze the reasons for the risk of renal insufficiency in CD patients. Patients and Methods: Among the 1500 patients of our tertiary center for CD we found eight patients (four female, four male; median age at diagnosis of CD: 33.5 years, range: 19 to 57; median duration at of CD at the time of onset of renal insufficiency: 21.5 years, range: 15 to 26; median age at diagnosis of renal insufficiency: 60.5 years, range: 39 to 73) suffering from renal impairment with permanently elevated creatinine serum levels above 1.5mg/100ml (median current creatinine level: 4.1mg/100ml). Four of those needed regular hemodialysis. Two of the patients had died. We matched those patients respectively with two CD patients of same sex, age at diagnosis and duration of disease, but normal kidney function. The medical histories of all patients were carefully reviewed and data were analyzed by Mann-Whitney-U or Fisher's exact test where appropriate. Results: Out of 8 patients with renal insufficiency 2 patients (29%) had L3 location of CD and 5 (71%) L4, in the control group 6 patients (43%) had L3 and 8 (57%) L4 (Vienna Classification). One patient developed renal insufficiency due to amyloidosis and one as a consequence of a nephrectomy due to fistulizing disease. No patient showed hypertension before onset of renal impairment. The median number of resected colonic segments in the group of patients with renal insufficiency was 2 (range 0 to 4), in the control group 0 (range 0 to 5), the median length of resected small bowel was 80cm (range: 20 to 340cm), controls: 65.5cm (range: 0 to 290cm), the median duration of 5-aminosalicylates at onset of renal impairment was 66 months (range: 0 to 264 months), controls: 19.5 months (range: 0 to 252 months) and the number of previous kidney stone lithotrypsies was 1 (range: 0 to 20), control: 0 (range: 0 to 6). There was no significant difference between both groups regarding these parameters. Conclusion: Patients with longstanding CD show a considerable risk for terminal renal insufficiency. Although we were not able to detect one single cause of renal insufficiency in patients with CD, it is evident, that the risk increases with the duration of disease, because all patients had a minimum duration of 15 years. This makes it more probable, that renal insufficiency may be a consequence of CD itself.

Biochemical parameters as prognostic factors in prostatic adenocarcinoma.

The serum levels of creatinine (CR), alkaline phosphatase (ALP), acid phosphatase (ACP) and tartrate inhibitable acid phosphatase (TIAP) were related to Gleason score, TM-category, disease progression and survival in 325 prostatic adenocarcinoma patients followed up for over 12 years. Elevated serum levels of CR, ALP, ACP and TIAP were related to invasive and metastatic disease as well as with a high Gleason score. Elevated serum levels of CR, ALP, ACP and TIAP, all significantly predicted prognosis in a univariate analysis. In the M0 tumours, ACP and TIAP and TIAP had prognostic value, as they did in the T1-2M0 tumours respectively. Cox's multivariate analysis showed that serum creatinine level at diagnosis had independent prognostic value additional to the TM-classification, Gleason score and patient age. In the M0 tumours, ALP had independent prognostic significance additional to the T-category, Gleason score and patient age. In the T1-2M0 tumours, TIAP had independent prognostic value supplementary to the Gleason score, T-category and patient age, whereas in the T1M0 tumours, the gleason score was an independent prognostic parameter. The results indicate that these simple laboratory tests give important prognostic information in prostatic adenocarcinoma.

QUALITY ASSURANCE OF DRUG THERAPY IN HOSPITALS:

A programme for the systematic adjustment of drug dosage in hospital patients with impairment of renal function is described. This programme involves the efficient identification of patients with elevated serum levels of creatinine, the checking of dosage regimens for these patients in terms of known pharmacokinetic data, and advising of medical officers when dosage regimens are in excess of those recommended, or where contraindicated drugs have been prescribed. The procedure, which has been shown to be both workable and effective in a large teaching hospital over a period of more than two years, serves as a model for quality assurance of an aspect of drug treatment with existing staff and with no additional capital costs.