Elevated Blood Urea Nitrogen Levels Research Articles

Kidney Function Status in Nigerian Human Malaria Patients

Malaria is now known to affect over 500 million persons worldwide, killing about 1 to 3 million of them annually. Plasmodium falciparum is the species mostly implicated in the causation of severe malaria. This study was carried out to investigate the kidney function status of malaria patients in Benin metropolis, Southern Nigeria, to ascertain if there is renal dysfunction/impairment in them. Plasma levels of sodium, potassium, bicarbonate, urea, creatinine and blood urea nitrogen (BUN) were assayed in a total of 152 subjects (112 malaria patients infected with Plasmodium falciparum and 40 controls) of both sexes, with their age ranging from 8 to 42 years. The results observed irrespective of age or sex, reveal a statistically significant (p<0.05) increase in plasma levels of potassium, urea, BUN and creatinine (4.49±0.95 mmol/L;5.88±0.13mmol /L;16.39±0.36mg/dl and 135.05±2.69imol/L) when compared to their controls (4.05±0.34mmol/L;3.73±0.12mmol/L;10.34±0.36mg/dl and 80.71±1.69imol/L, respectively) and also a statistically significant (P<0.05) reduction in plasma levels of Na+ and HC03- (128.50±0.77 and 19.98±0.28mmol/L) when compared to their controls (l38.58±0.29 and 24.70±0.36mmol/L, respectively). The hyponatraemia and metabolic acidosis observed in the malaria patients are negatively correlated with the degree of parasitaemia (r=-0.241 and r=-0.019, respectively), while the elevated plasma potassium and creatinine levels are positively correlated with the degree of parasitaemia (r=0.153 and r=0.407, respectively). The elevated plasma Urea and BUN levels are also positively correlated with the degree of parasitaemia (r=0.371 and r=0.375, respectively). The results of this study indicate that there is significant renal dysfunction/impairment in patients in southern Nigeria infected with plasmodium falciparum. Keywords : Malaria infection, Kidney function status.

Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation

The coordination of multiple cytokines and transcription factors with their downstream signaling pathways have been shown to be integral to nephron maturation. Here we present a completely novel role for the helix-loop-helix transcription factor Early B cell Factor 1 (Ebf1), originally identified for B cell maturation, for the proper maturation of glomerular cells from mesenchymal progenitors. The expression of Ebf1 was both spatially and temporally regulated within the developing cortex and glomeruli. Using Ebf1-null mice we then identified biochemical, metabolic, and histological abnormalities in renal development that arose in the absence of this transcription factor. In the Ebf1 knockout mice the developed kidneys show thinned cortices and reduced glomerular maturation. The glomeruli showed abnormal vascularization and severely effaced podocytes. The mice exhibited early albuminuria and elevated blood urea nitrogen levels. Moreover, the GFR was reduced over 66 percent and the expression of podocyte-derived VEGF-A was decreased compared to wild type control mice. Thus, Ebf1 has a significant and novel role in glomerular development, podocyte maturation, and the maintenance of kidney integrity and function.

Betaine supplementation protects against renal injury induced by cadmium intoxication in rats: Role of oxidative stress and caspase-3

Cadmium (Cd) is an environmental and industrial pollutant that can induce a broad spectrum of toxicological effects that affect various organs in humans and experimental animals. This study aims to investigate the effect of betaine supplementation on cadmium-induced oxidative impairment in rat kidney. The animals were divided into four groups (n=10 per group): control, cadmium, betaine and betaine+cadmium (1) saline control group; (2) cadmium group in which cadmium chloride (CdCl2) was given orally at a daily dose of 5mg/kg body weight for four weeks; (3) betaine group, in which betaine was given to rats at a dose of 250mg/kg/day, orally via gavage for six weeks; (4) cadmium+betaine group in which betaine was given at a dose of 250mg/kg/day, orally via gavage for two weeks prior to cadmium administration and concurrently during cadmium administration for four weeks. Cadmium nephrotoxicity was indicated by elevated blood urea nitrogen (BUN) and serum creatinine levels. Kidneys from cadmium-treated rats showed an increase in lipid peroxidation measured as thiobarbituric acid-reactive substances (TBARS) concentration and reductions in total antioxidant status (TAS), reduced glutathione (GSH) content, glutathione peroxidase (GSH-Px) activity, superoxide dismutase concentration (SOD) and catalase activity. Caspase-3 activity, a marker of DNA damage was also elevated in renal tissues of cadmium-treated rats. Pre-treatment of rats with betaine substantially attenuated the increase in BUN and serum creatinine levels. Betaine also inhibited the increase in TBARS concentration and reversed the cadmium-induced depletion in total antioxidant status, GSH, GSH-Px, SOD and catalase concentrations in renal tissues. Renal caspase-3 activity was also reduced with betaine supplementation. These data emphasize the importance of oxidative stress and caspase signaling cascade in cadmium nephrotoxicity and suggest that betaine pretreatment reduces severity of cadmium nephrotoxicity probably via antioxidant action and suppression of apoptosis.

A Case of Acute Kidney Injury in a Patient with Pulmonary Tuberculosis Receiving Ethambutol Therapy

Ethambutol is commonly used as a first-line drug for the treatment of tuberculosis. The most serious adverse effect of ethambutol therapy is optic neuropathy. However, ethambutol-induced acute kidney injury is extremely rare. We report herein a case of acute kidney injury secondary to ethambutol-associated acute interstitial nephritis. A 65-year-old man with pulmonary tuberculosis presented with a > 7-day history of nausea and vomiting. He had begun antituberculosis medications including ethambutol 3 weeks previously. His laboratory findings showed elevated blood urea nitrogen and serum creatinine levels (32.6 and 3.6 mg/dL, respectively). Examination of percutaneous renal biopsy specimens showed diffuse interstitial mononuclear cell infiltration with mild interstitial edema. The patient was treated by cessation of ethambutol and supportive care. His renal function completely recovered (creatinine, 1.1 mg/dL) and his clinical symptoms improved. (Korean J Med 2014;87:352-356)

Prognostic impact of renal function in precapillary pulmonary hypertension

Impairment of renal function is associated with adverse outcome in various diseases. Patients with pulmonary hypertension (PH) show diminished cardiac function and organ perfusion. The aim of this study was to investigate the associations between renal function and both haemodynamic parameters and long-term survival in patients with PH. Blood was collected from 64 patients with PH (Dana Point class 1, 3 and 4) during right heart catheterization, and plasma was prepared. Creatinine, blood urea nitrogen (BUN), cystatin C, neutrophil-gelatinase-associated lipocalin (NGAL), fibroblast growth factor 23 (FGF-23) and α-Klotho levels were determined, and glomerular filtration rate (GFR) was estimated (eGFR). Parameters were evaluated using c-statistics and dichotomized for survival analysis based on receiver operating characteristic curves. The median follow-up time was 9.92 years with all-cause mortality as the primary end-point. Elevated BUN, cystatin C and creatinine levels were associated with decreased survival, with hazard ratios (HRs) of 3.237, 4.514 and 2.006, respectively, and equivalent performance according to c-statistics. Estimating GFR by CKD-EPI, MDRD and Cockcroft-Gault formulas resulted in HRs of 2.942, 2.694 and 3.306, respectively. Amongst these formulas, eGFR (Cockcroft-Gault) had the highest c-statistics of 0.674. There was a correlation between BUN and both cardiac index (τ = -0.39) and pulmonary vascular resistance index (τ = 0.249), whereas eGFR (CKD-EPI) was correlated with cardiac index (τ = 0.225). No correlations between either BUN or eGFR and right atrial pressure (RAP) were observed. NGAL, FGF-23 and α-Klotho had no prognostic impact or association with haemodynamic parameters. Comparison of markers of renal function for prognosis in PH demonstrated superiority of creatinine, cystatin C and BUN over NGAL, FGF-23 and α-Klotho. Minor decreases in eGFR influence long-term prognosis, and measurement of cystatin C levels might be useful to detect renal impairment in patients with a normal serum concentration of creatinine. Renal function in patients with PH is linked to cardiac index rather than RAP.

Persistent Low Level of Osterix Accelerates Interleukin-6 Production and Impairs Regeneration after Tissue Injury

Osterix (Osx) is an essential transcription factor for osteoblast differentiation and bone formation. Osx knockout show a complete absence of bone formation, whereas Osx conditional knockout in osteoblasts produce an osteopenic phenotype after birth. Here, we questioned whether Osx has a potential role in regulating physiological homeostasis. In Osx heterozygotes expressing low levels of Osx in bones, the expression levels of pro-inflammatory cytokines were significantly elevated, indicating that reduced Osx expression may reflect an inflammatory-prone state. In particular, the expression of interleukin-6, a key mediator of chronic inflammation, was increased in Osx heterozygotes and decreased in Osx overexpressing osteoblasts, and transcriptionally down-regulated by Osx. Although no significant differences were revealed in renal morphology and function between Osx heterozygotes and wild-type under normoxic conditions, recovery of kidneys after ischemic damage was remarkably delayed in Osx heterozygotes, as indicated by elevated blood urea nitrogen and creatinine levels, and by morphological alterations consistent with acute tubular necrosis. Eventually, protracted low Osx expression level caused an inflammatory-prone state in the body, resulting in the enhanced susceptibility to renal injury and the delayed renal repair after ischemia/reperfusion. This study suggests that the maintenance of Osx expression in bone is important in terms of preventing the onset of an inflammatory-prone state.

Mortality differences among hospitalized patients with community-acquired pneumonia in three world regions: Results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

Community-acquired pneumonia (CAP) causes considerable worldwide mortality, but limited data compare the mortality in different regions of the world. Our objective was to determine if there was a difference in mortality among hospitalized patients with CAP in three continental regions of the world. This was a cohort study of patients hospitalized for CAP between November 2001 and December 2011 from 70 institutions in 16 countries in US/Canada, Europe and Latin America; the Community-Acquired Pneumonia Organization (CAPO) international database. The primary outcome was mortality, and factors of interest included world region, processes of care, severity of disease, associated pathogen, specific comorbidities, and antimicrobial therapy. Multivariable logistic regression was performed to adjust for confounding effects on differences in mortality between regions. Patients were analyzed separately based on their intensive care unit admission status. A total of 6371 patients were reviewed. Latin America had the highest mortality (13.3%) followed by Europe (9.1%) and the USA/Canada (7.3%) (P<0.001 for differences between regions). Important confounding variables included comorbidities (i.e., congestive heart failure, cerebrovascular disease), elevated blood urea nitrogen level, antimicrobial therapy (macrolide or fluoroquinolone use), and whether the patient had prior vaccinations (influenza, pneumococcal). After adjustment for confounding variables, estimated differences in mortality between the three regions were significantly reduced for both patients in the ICU and the ward. There was an observed discrepancy in CAP mortality between three world regions. Identified factors that contributed to these differences included incidence of H1N1 infection, elevated BUN, cerebrovascular disease, macrolide use, fluoroquinolone use, and vaccinations. Treatment regimen (fluoroquinolone and macrolide use) and preventive measures (vaccinations) were variables that may be modified to help alleviate the differences.

Histological, ultrastructural and immunohistochemical studies on the protective effect of ginger extract against cisplatin-induced nephrotoxicity in male rats.

Cisplatin (CP) is a widely used anticancer drug; however, it has several side effects such as nephrotoxicity. Ginger, the rhizome of Zingiber officinale, consumed since ancient times has numerous health benefits. The objective of this work was to evaluate the protective effect of ginger extract (GE) against CP-induced nephrotoxicity. CP group displayed a marked renal failure characterized by a significant increase in serum creatinine and blood urea nitrogen (BUN) levels in addition to severe histopathological and ultrastructural renal alterations. Also, CP group showed an increase in the immunohistochemical expression of Bax proapoptotic protein. In contrast, GE+CP group showed significant decrease in the elevated serum creatinine and BUN levels and an improvement in the histopathological and ultrastructural renal injury induced by CP. The overexpression of Bax proapoptotic protein was significantly decreased in the GE+CP group. Hence, the present results indicated that GE has a protective effect against CP-induced renal damage in rats. Thereby, such findings recommended the usage of GE to prevent and/or decrease the renal damage induced by CP chemotherapeutic treatment.

Generation of c-Myc transgenic pigs for autosomal dominant polycystic kidney disease

After several decades of research, autosomal dominant polycystic kidney disease (ADPKD) is still incurable and imposes enormous physical, psychological, and economic burdens on patients and their families. Murine models of ADPKD represent invaluable tools for studying this disease. These murine forms of ADPKD can arise spontaneously, or they can be induced via chemical or genetic manipulations. Although these models have improved our understanding of the etiology and pathogenesis of ADPKD, they have not led to effective treatment strategies. The mini-pig represents an effective biomedical model for studying human diseases, as the pig's human-like physiological processes help to understand disease mechanisms and to develop novel therapies. Here, we tried to generate a transgenic model of ADPKD in pigs by overexpressing c-Myc in kidney tissue. Western-blot analysis showed that c-Myc was overexpressed in the kidney, brain, heart, and liver of transgenic pigs. Immunohistochemical staining of kidney tissue showed that exogenous c-Myc predominantly localized to renal tubules. Slightly elevated blood urea nitrogen levels were observed in transgenic pigs 1 month after birth, but no obvious abnormalities were detected after that time. In the future, we plan to subject this model to renal injury in an effort to promote ADPKD progression.

Deficit of p66ShcA restores redox-sensitive stress response program in cisplatin-induced acute kidney injury

Overwhelming oxidative stress and compromised tubular cell antioxidant response have been incriminated for cisplatin (Cis)-induced acute kidney injury (AKI). We hypothesized that Cis-induced AKI was the outcome of the deactivated redox-sensitive stress response program (RSSRP). Wild type (WT) and heterozygous p66ShcA(p66+/−) mice in groups of six were administered either normal saline (WT) or Cis (12.5mg/kg, intraperitoneal, Cis/WT). Renal biomarkers were collected and kidneys were harvested for renal histology. Cis/WT showed elevated blood urea nitrogen levels and enhanced tubular cell apoptosis, necrosis, and dilated tubules filled with casts when compared to Cis/p66+/−. Cis/p66+/− developed only a clinically occult AKI (normal blood urea levels and only microscopic alterations). Immunoblots from the lysates of renal tissues of Cis/WT displayed enhanced expression of phospho-p66ShcA, and phospho-Foxo3A but attenuated expression of MnSOD and catalase; conversely, p66 deficit prevented these alterations in Cis milieu. In in vitro studies, Cis treated mouse proximal tubular cells (MPTCs) displayed enhanced phosphorylation of p66ShcA and no increase in tubular cell expression of MnSOD. In addition, renal tissues of Cis/WT and Cis-treated MPTCs displayed enhanced phosphorylation of p53 and Bax expression. However, MPTC partially silenced for p66ShcA displayed partial inhibition of Cis-induced tubular cell apoptosis as well as necrosis. These findings indicate that Cis-induced AKI is the outcome of the deactivated RSSRP (attenuated anti-oxidant response) and activation of pro-apoptotic (p53-induced Bax expression) pathway.

Assessment of cisplatin-induced kidney injury using an integrated rodent platform

Current diagnosis of drug-induced kidney injury (DIKI) primarily relies on detection of elevated plasma creatinine (Cr) or blood urea nitrogen (BUN) levels; however, both are indices of overall kidney function and changes are delayed with respect to onset of nephron injury. Our aim was to investigate whether early changes in new urinary DIKI biomarkers predict plasma Cr, BUN, renal hemodynamic and kidney morphological changes associated with kidney injury following a single dose of cisplatin (CDDP) using an integrated platform in rodent. Conscious surgically prepared male Han Wistar rats were given a single intraperitoneal dose of CDDP (15mg/kg). Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), urinalysis, DIKI biomarkers, CDDP pharmacokinetics, blood pressures, heart rate, body temperature and electroencephalogram (EEG) were measured in the same vehicle- or CDDP-treated animals over 72h. Plasma chemistry (including Cr and BUN) and renal tissues were examined at study termination. Cisplatin caused progressive reductions of GFR, ERPF, heart rate and body temperature from day 1 (0–24h). DIKI biomarkers including alpha-glutathione S-transferase (α-GST) significantly increased as early as 6h post-dose, which preceded significant declines of GFR and ERPF (24h), increased plasma Cr and BUN (72h), and associated with renal acute tubular necrosis at 72h post-dose. The present study adds to the current understanding of CDDP action by demonstrating that early increases in urinary excretion of α-GST predict DIKI risk following acute exposure to CDDP in rats, before changes in traditional DIKI markers are evident.

The Protective Effects of Apocynin on Kidney Damage Caused by Renal Ischemia/Reperfusion

This experimental study was designed to explore the protective effect of apocynin, the NADPH-oxidase inhibitor, on kidney damage induced by ischemia/reperfusion (I/R) in a rat model. Thirty-two rats were randomly divided into a control group and three I/R groups (1-hour ischemia followed by 23-hour reperfusion). Three I/R groups were treated by apocynin (20 mg/kg, i.p.) at two different time points (before ischemia and during ischemia). The histopathological findings, including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathion peroxidase (GPX), reduced glutathione (GSH), myeloperoxidase (MPO), blood urea nitrogen (BUN), and serum creatinine (Cr) levels, were determined. Kidney tissue MDA and MPO, and serum BUN and Cr levels were found to be significantly higher in the I/R group, but there was no statistically significant difference in the levels of SOD, CAT, GPX, and GSH between the I/R and the control groups. Although apocynin significantly reduced MDA and MPO in group 3 and increased GPX in both treatment groups when compared to the I/R group, the elevated BUN and Cr levels were significantly reduced in treatment groups. Renal I/R injury also induced extensive tubular necrosis, glomerular damage, and apoptosis in the histological evaluation. Apocynin, especially when used during ischemia, ameliorated these histological damages in different amounts in treatment groups. The beneficial effects of apocynin on renal I/R injury were evaluated for the first time.

Hesperidin attenuates cisplatin-induced acute renal injury by decreasing oxidative stress, inflammation and DNA damage

Nephrotoxicity is an important complication in cancer patients undergoing cisplatin therapy. Oxidative stress, inflammation and apoptosis/necrosis are the major patho-mechanisms of cisplatin induced nephrotoxicity. In the present study, hesperidin, a naturally-occurring bioflavonoid has been demonstrated to have protective effect on cisplatin-induced renal injury in rats. Cisplatin intoxication resulted in structural and functional renal impairment which was revealed by massive histopathological changes and elevated blood urea nitrogen and serum creatinine levels, respectively. Renal injury was associated with oxidative stress/lipid peroxidation as evident by increased reactive oxygen species (ROS) and malondialdehyde (MDA) formation with decreased levels of antioxidants such as reduced glutathione, vitamin C, catalase, superoxide dismutase, glutathione reductase, glutathione peroxidase and glutathione-S-transferase. Cisplatin administration also triggered inflammatory response in rat kidneys by inducing pro-inflammatory cytokine, TNF-α, with the increased expression of myeloperoxidase (MPO). Furthermore, cisplatin increased the activity of caspase-3 and DNA damage with decreased tissue nitric oxide levels. Hesperidin treatment significantly attenuated the cisplatin-induced oxidative stress/lipid peroxidation, inflammation (infiltration of leukocytes and pro-inflammatory cytokine), apoptosis/necrosis (caspase-3 activity with DNA damage) as well as increased expression of nitric oxide in the kidney and improved renal function. Thus, our results suggest that hesperidin co-administration may serve as a novel and promising preventive strategy against cisplatin-induced nephrotoxicity.

Acute renal failure caused by severe coagulopathy induced by the interaction between warfarin potassium and levofloxacin: a case report

To the Editor: A 30-year-old man took warfarin potassium (4 mg/day) for several years because of idiopathic dilated cardiomyopathy (ejection fraction was 48 %, and no arrhythmia was observed). His medical regimen included aspirin (100 mg/day), digoxin (0.25 mg/day), pimobendan (20 mg/day), and atenolol (50 mg/day); glimepiride (4 mg/day), voglibose (2.7 mg/day), and allopurinol (900 mg/day) (for diabetes mellitus and hyperuricemia); and milnacipran hydrochloride (25 mg/day), fluvoxamine maleate (200 mg/day), risperidone (2 mg/day), and sodium valproate (800 mg/day) (for Asperger’s syndrome). Despite the long-term use of these medicines, neither renal disorders nor bleeding tendencies were observed [prothrombin time (PT)-international normalized ratio (INR) (PT-INR) was controlled around 1.5]. The patient presented to the emergency room with hematuria. Laboratory analyses indicated elevated white blood cell counts (20,500 cells/m) and C-reactive protein levels (4.5 mg/dl), but no anemia. We suspected urinary tract infection; therefore, levofloxacin (900 mg/day) was prescribed. After 6 days, the patient was brought to the emergency room because of hypovolemic shock resulting from nasal hemorrhage (Hb 3.7 mg/dl, Hct 10.9 %). Prothrombin time (PT) could not be determined. Acute renal failure (ARF) was suspected because of elevated blood urea nitrogen (100 mg/dl), creatinine (6.2 mg/dl), and serum potassium (6.2 mmol/l) levels. Severe hematuria with a distinct blood clot was observed. Warfarin and aspirin were discontinued; vitamin K (20 mg) was administered. Under strict observation for volume overload, Ringer’s solution and washed red cells were administered. Sufficient spontaneous urine production was maintained. Renal function recovered without hemodialysis. The hypovolemic shock caused by nasal bleeding and severe hematuria resulted in prerenal ARF; the hematoma that obstructed the urinary tract resulted in postrenal ARF. We believed both preand postrenal ARF were present. The patient’s course of PTINR and creatinine values is shown in Fig. 1. The patient had been taking warfarin for 3 years. Bleeding improved with vitamin K; therefore, the cause of coagulopathy was thought to be reinforced by the effects of warfarin. Several drugs interact with warfarin [1]. We suspected that valproate, allopurinol, and levofloxacin could interact with warfarin. ARF may have caused elevated plasma valproate and allopurinol concentrations, which could have then interacted with warfarin. However, valproate and allopurinol previously had been taken routinely, without bleeding tendencies. Thus, the newly prescribed levofloxacin was mainly responsible for this coagulopathy. Ofloxacin suppress the propagation of vitamin K-producing enteric bacteria, and thus the effects of warfarin would be enhanced. Also, warfarin and ofloxacin competitively bind with protein. Thus, the free effect of warfarin increases with the use of ofloxacin [2]. Levofloxacin and ofloxacin are both C. Nemoto (&) Y. Ikegami J. Shimada Y. Tsukada Y. Abe C. Tase Department of Critical Care and Emergency Medicine, Fukushima Medical University, 1-Hikarigaoka, Fukushima 960-1295, Japan e-mail: nemo@fmu.ac.jp

Hydronephrosis associated with ureteral wall thickness: Question

A 12-year old male patient presented for elevated blood urea nitrogen and creatinine levels that were noticed during evaluation for anorexia, vomiting and weight loss for the preceding 2 weeks. Past medical history was characterized by right hydronephrosis determined 6 months ago upon evaluation for flank pain. At that time, although imaging tests had suggested suspicious right lower ureteral stone, cystoscopy had revealed fibrotic changes without stone in the lower right ureter. A temporary ureteral stent had been placed and removed during follow up. Physical examination was normal apart from pallor. Laboratory tests revealed normal urinalysis, low hemoglobin (8.5 g/dL), low MCV (74.5 fL), elevated acute phase response (erythrocyte sedimentation rate 54 mm/h, C-reactive protein 17.5 mg/L), impaired renal functions (BUN 23 mg/ dL, creatinine 2.34 mg/dL, creatinine clearance 30 mL/min/ 1.73 m, fractional Na excretion 3.6 %). Urinary system ultrasonography (USG) showed bilateral hydroureteronephrosis and increased renal echogenity. Magnetic resonance (MR) urography disclosed increased wall thickness in all segments of right ureter. Diagnostic ureteroscopy and retrograde pyelography revealed segmental areas of stenosis in both ureters (Fig. 1) and both ureters were catheterized. Renal functions were normalized shortly afterwards. Diagnostic tests for the diseases associated with ureteral wall thickening including urine culture, PPD skin test, chest X-ray, immunological tests for vasculitides and MEFV gene mutation screening were normal.

Role of genetic modifiers in an orthologous rat model of ARPKD

Human data and animal models of autosomal recessive polycystic kidney disease (ARPKD) suggest that genetic factors modulate the onset and severity of the disease. We report here for the first time that ARPKD susceptibility is attenuated by introgressing the mutated Pkhd1 disease allele from the polycystic kidney (PCK) rat onto the FHH (Fawn-Hooded Hypertensive) genetic background. Compared with PCK, the FHH.Pkhd1 strain had significantly decreased renal cyst formation that coincided with a threefold reduction in mean kidney weights. Further analysis revealed that the FHH. Pkhd1 is protected from increased blood pressure as well as elevated plasma creatinine and blood urea nitrogen levels. On the other hand, liver weight and biliary cystogenesis revealed no differences between PCK and FHH.Pkdh1, indicating that genes within the FHH genetic background prevent the development of renal, but not hepatic, manifestations of ARPKD. Microarray expression analysis of kidneys from 30-day-old PCK rats revealed increased expression of genes previously identified in PKD renal expression profiles, such as inflammatory response, extracellular matrix synthesis, and cell proliferation genes among others, whereas the FHH.Pkhd1 did not show activation of these common markers of disease. This newly developed strain can serve as a tool to map modifier genes for renal disease in ARPKD and provides further insight into disease variability and pathophysiology.

Pediatric Systemic Lupus Erythematosus: More Than a Positive Antinuclear Antibody

Based on strong research evidence and consensus, the most common disease manifestations at diagnosis of pSLE are constitutional symptoms, arthritis, and malar rash. Based on some research evidence and consensus, patients with pSLE tend to have major organ system involvement (renal/central nervous system) and a greater disease burden compared with adults. Despite these findings, mortality is low. Based on some research evidence and consensus, the diagnosis of pSLE is unlikely if the ANA is negative, and most patients with SLE have a positive ANA at a titer ≥1:160. Based on strong research evidence, both MMF and cyclophosphamide can be used for induction therapy in class III and IV lupus nephritis. Based on strong research evidence, patients with SLE and anticardiolipin antibodies or LA have a two and six times greater risk of venous thrombosis, respectively, compared with patients with SLE without antiphospholipid antibodies. Based on strong research evidence, patients with pSLE have a higher risk for subclinical atherosclerosis when there is weight-adjusted prednisone use, azathioprine use, increasing age, male gender, high BMI, abnormal creatinine clearance, and elevated lipoprotein(a) levels.

Elevated Blood Urea Nitrogen Is a Predictive Factor for Intensive Care Unit Admission in Legionella Pneumonia

Background : Legionella pneumonia (L. pneumonia) is a serious disease among patients with community-acquired pneumonia (CAP). Appropriate initial assessment of severity and admission to intensive care unit (ICU) can reduce mortality due to L. pneumonia. Here, the efficacy of using the current CAP scoring for recommending admission to ICU and other variables for initial management were evaluated. Methods : The clinical characteristics of 11 patients diagnosed with L. pneumonia at Maebashi Red Cross Hospital from November 1999 to July 2010 were examined. The scoring systems of A-DROP (A : Age, D : Dehydration, R : Respiration, O : Orientation, and P : Blood Pressure) and CURB-65 (C : Confusion, U : Urea, R : Respiratory rate, B : Blood pressure, and Age) were used. Results : Of the 11 L. pneumonia patients, 6 were admitted to the ICU. By A-DROP and CURB-65 scoring systems, 4 cases were assessed as not severe. Among the parameters used in the scores, only elevated blood urea nitrogen (BUN) had significantly predictive potential for ICU admission (sensitivity=100%, specificity=80%, P< 0.02). Both A-DROP and CURB-65 scoring systems underestimated the severity of CAP caused by L. spp .. Conclusions : In the case of L. pneumonia, elevated BUN level is important for assessing CAP severity and making ICU admission recommendations.

Protective Effect of Dexpanthenol on Ischemia-Reperfusion-Induced Renal Injury in Rats

Background/Aims: This experimental study was designed to investigate protective and therapeutic effects of Dexpanthenol (Dxp), an alcoholic analogue of pantothenic acid, on kidney damage induced by ischemia-reperfusion (I/R) in rats. Methods: Forty rats were randomly divided into a control group and 4 I/R groups (1 h ischemia followed by 23 h reperfusion). Three I/R groups were treated by Dxp (500 mg/kg, i.p.) at 3 different time points (before ischemia, during ischemia and late reperfusion). The histopathological findings including apoptotic changes, and also tissue malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), blood urea nitrogen (BUN), serum creatinine (Cr) and albumin (Alb) levels were determined. Results: Kidney tissue MDA levels were found to be significantly higher in the I/R group, whereas the values of GPX were lower when compared to the control group. The levels of SOD and CAT did not reach to statistical meaning level in I/R group. Dxp given during ischemia reduced the elevated MDA levels to the nearly control levels and this ameliorating effect was found as parallel to the result of GPX. Serum levels of BUN and Cr were significantly higher in I/R group. Dxp given during ischemia significantly reduced the elevated BUN and Cr levels when compared to I/R group. Renal I/R injury also induced extensive tubular necrosis, glomerular damage and apoptosis in the histological evaluation. Dxp ameliorated these histological damages in different amounts in all treatment groups. Conclusion: In this study the protective effects of Dxp against renal I/R injury has been evaluated for the first time.

Interaction Between Loop Diuretic-Associated Mortality and Blood Urea Nitrogen Concentration in Chronic Heart Failure

The purpose of this study was to investigate whether a surrogate for renal neurohormonal activation, blood urea nitrogen (BUN), could identify patients destined to experience adverse outcomes associated with the use of high-dose loop diuretics (HDLD). Loop diuretics are commonly used to control congestive symptoms in heart failure; however, these agents cause neurohormonal activation and have been associated with worsened survival. Subjects in the BEST (Beta-Blocker Evaluation of Survival Trial) receiving loop diuretics at baseline were analyzed (N = 2,456). The primary outcome was the interaction between BUN- and HDLD-associated mortality. In the overall cohort, HDLD use (≥160 mg/day) was associated with increased mortality (hazard ratio [HR]: 1.56; 95% confidence interval [CI]: 1.35 to 1.80). However, after extensively controlling for baseline characteristics, this association did not persist (HR: 1.06; 95% CI: 0.89 to 1.25). In subjects with BUN levels above the median (21.0 mg/dl), both the unadjusted (HR: 1.59; 95% CI: 1.34 to 1.88) and adjusted (HR: 1.29; 95% CI: 1.07 to 1.60) risk of death was higher in the HDLD group. In patients with BUN levels below the median, there was no associated risk with HDLD (HR: 0.99; 95% CI: 0.75 to 1.34) and after controlling for baseline characteristics, the HDLD group had significantly improved survival (HR: 0.71; 95% CI: 0.49 to 0.96) (p interaction = 0.018). The risk associated with HDLD use is strongly dependent on BUN concentrations with reduced survival in patients with an elevated BUN level and improved survival in patients with a normal BUN level. These data suggest a role for neurohormonal activation in loop diuretic-associated mortality.