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Renal function in patients with β-thalassaemia major: a long-term follow-up study.

Tue, 07/09/2013 - 10:26
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Renal function in patients with β-thalassaemia major: a long-term follow-up study.

Nephrol Dial Transplant. 2012 Sep;27(9):3547-51

Authors: Lai ME, Spiga A, Vacquer S, Carta MP, Corrias C, Ponticelli C

Abstract
BACKGROUND: Little information is available about the kidney's involvement in patients with β-thalassaemia major (TM). In particular, there are no studies reporting the outcome of renal function over time.
METHODS: In this retrospective study, we evaluated the changes in estimated glomerular filtration rate (eGFR) in 81 adult patients with TM followed for 10 years. Only patients who had an eGFR of >90 mL/min/1.73 m(2) at presentation were admitted to the study. All patients were regularly followed for at least 10 years.
RESULTS: At 10 years, 66 patients showed a mild decline in eGFR that remained, however, within a normal range (from 119.9 to 113.6 mL/min/1.73 m(2), P = 0.636). In the remaining 15 patients (18.5%), eGFR decreased to <90 mL/min (from 98.1 to 78.2 mL/min/1.73 m(2); P = 0.004). The repeated-measures models showed that the decline in eGFR over time was significantly higher (P = 0.0068) in patients with baseline phosphaturia >1000 mg/24 h (P = 0.0068), while eGFR tended to decline more rapidly in patients with baseline uricuria >700 mg/24 h than in those with lower uricuria (P = 0.0783). Univariate Cox's proportional regression models showed that abnormal levels of calcaemia were associated with the risk of kidney damage [hazard ratio (HR) 0.30, 95% confidence interval 0.09-0.97 for calcaemia 8.4-10.2 mg/dL versus HR not estimable for calcaemia <8.4 or >10.2 mg/dL].
CONCLUSIONS: In most adults with TM, the eGFR tends to remain within a normal range after 10 years. However, patients with elevated phosphaturia, elevated uricuria and/or abnormal levels of calcaemia show a significant decline in eGFR over time, suggesting that tubular damage acquired in childhood caused by either TM or its treatment may eventually result in abnormal eGFR. Further studies in a larger cohort of TM patients are needed to further elucidate the long-term impact of TM on renal function.

PMID: 22695832 [PubMed - indexed for MEDLINE]

Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial.

Tue, 07/09/2013 - 10:26
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Predictors of haemoglobin levels and resistance to erythropoiesis-stimulating agents in patients treated with low-flux haemodialysis, haemofiltration and haemodiafiltration: results of a multicentre randomized and controlled trial.

Nephrol Dial Transplant. 2012 Sep;27(9):3594-600

Authors: Locatelli F, Altieri P, Andrulli S, Sau G, Bolasco P, Pedrini LA, Basile C, David S, Feriani M, Nebiolo PE, Ferrara R, Casu D, Logias F, Tarchini R, Cadinu F, Passaghe M, Fundoni G, Villa G, Di Iorio BR, Zoccali C

Abstract
BACKGROUND: Predictors of haemoglobin (Hb) levels and resistance to erythropoiesis-stimulating agents (ESAs) in dialysis patients have not yet been clearly defined. Some mainly uncontrolled studies suggest that online haemodiafiltration (HDF) may have a beneficial effect on Hb, whereas no data are available concerning online haemofiltration (HF). The objectives of this study were to evaluate the effects of convective treatments (CTs) on Hb levels and ESA resistance in comparison with low-flux haemodialysis (HD) and to evaluate the predictors of these outcomes.
METHODS: Primary multivariate analysis was made of a pre-specified secondary outcome of a multicentre, open-label, randomized controlled study in which 146 chronic HD patients from 27 Italian centres were randomly assigned to HD (70 patients) or CTs: online pre-dilution HF (36 patients) or online pre-dilution HDF (40 patients).
RESULTS: CTs did not affect Hb levels (P = 0.596) or ESA resistance (P = 0.984). Hb correlated with polycystic kidney disease (P = 0.001), C-reactive protein (P = 0.025), ferritin (P = 0.018), ESA dose (P < 0.001) and total cholesterol (P = 0.021). The participating centres were the main source of Hb variability (partial eta(2) 0.313, P < 0.001). ESA resistance directly correlated with serum ferritin (P = 0.030) and beta2 microglobulin (P = 0.065); participating centres were again a major source of variance (partial eta(2) 0.367, P < 0.001). Transferrin saturation did not predict either outcome variables (P = 0.277 and P = 0.170).
CONCLUSIONS: In comparison with low-flux HD, CTs did not significantly improve Hb levels or ESA resistance. The main sources of variability were participating centres, ESA dose and the underlying disease.

PMID: 22622452 [PubMed - indexed for MEDLINE]

Outcome of patients with membranous lupus nephritis in Cape Town South Africa.

Tue, 07/09/2013 - 10:26
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Outcome of patients with membranous lupus nephritis in Cape Town South Africa.

Nephrol Dial Transplant. 2012 Sep;27(9):3509-15

Authors: Okpechi IG, Ayodele OE, Jones ES, Duffield M, Swanepoel CR

Abstract
BACKGROUND: The kidney is one of the major target organs affected by systemic lupus erythematosus. Although proliferative forms of lupus nephritis (LN) occur more frequently than membranous LN (MLN), the latter appears to have a more favourable outcome. Only a few studies have reported the outcome of patients with MLN.
METHODS: A retrospective analysis of patients with biopsy-confirmed MLN from a single centre in South Africa treated from 1st January 2000 to 31st December 2009.
RESULTS: The mean age of the patients (n = 42) at onset of LN was 35.0 ± 12.8 years with 73.8% of the patients being of mixed ancestry (coloureds). Eleven patients (26.2%) reached the composite end point of death or end-stage renal disease or persistent doubling of serum creatinine. The overall median survival and median renal survival times were 82.3 ± 15.5 months (95% confidence interval 52.0-112.6) and 84.5 ± 15.0 months (55.1-113.8), respectively. Also, 5-year event-free survival and renal survival were 64 and 71%, respectively. On multivariate analysis, systolic blood pressure (BP) during follow-up (P = 0.029), diastolic BP during follow-up (P = 0.020) and attainment of complete remission at 6 months (P = 0.033) were factors associated with the composite end points. Although treatment with chloroquine was not significantly associated with the composite end points (P = 0.05), we found that patients who received chloroquine had better renal survival compared with those who did not (P = 0.007).
CONCLUSIONS: The outcome of patients with MLN in Cape Town is poorer than for similar patients reported from other centres across the world. Better BP control may significantly influence outcome of disease in these patients.

PMID: 22610989 [PubMed - indexed for MEDLINE]

Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR.

Tue, 07/09/2013 - 10:26
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Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR.

Nephrol Dial Transplant. 2012 Sep;27(9):3606-14

Authors: Inrig JK, Sapp S, Barnhart H, Patel UD, Reddan D, Singh A, Califf RM, Szczech L

Abstract
BACKGROUND: Targeting a higher hemoglobin in patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesis-stimulating agent (ESA) dose and in hemoglobin were predictive of changes in blood pressure (BP) and whether these changes were associated with cardiovascular outcomes.
METHODS: In this secondary analysis of 1421 Correction of Hemoglobin and Outcomes in Renal Disease (CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobin with changes in diastolic BP (DBP) and systolic BP (SBP). Poisson modeling was performed to determine whether changes in hemoglobin and BP were associated with the composite end point of death or cardiovascular outcomes.
RESULTS: Monthly average DBP, but not SBP, was higher in participants in the higher hemoglobin arm. Increases in ESA doses and in hemoglobin were significantly associated with linear increases in DBP, but not consistently with increases in SBP. In models adjusted for demographics and comorbid conditions, increases in ESA dose (>0 U) and larger increases in hemoglobin (>1.0 g/dL/month) were associated with poorer outcomes [event rate ratio per 1000 U weekly dose per month increase 1.05, (1.02-1.08), P = 0.002 and event rate ratio 1.70 (1.02-2.85), P = 0.05, respectively]. However, increasing DBP was not associated with adverse outcomes [event rate ratio 1.01 (0.98-1.03), P = 0.7].
CONCLUSION: Among CHOIR participants, higher hemoglobin targets, increases in ESA dose and in hemoglobin were associated both with increases in DBP and with higher event rates; however, increasing DBP was not associated with adverse outcomes.

PMID: 22573238 [PubMed - indexed for MEDLINE]

Chest ultrasound and hidden lung congestion in peritoneal dialysis patients.

Tue, 07/09/2013 - 10:26
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Chest ultrasound and hidden lung congestion in peritoneal dialysis patients.

Nephrol Dial Transplant. 2012 Sep;27(9):3601-5

Authors: Panuccio V, Enia G, Tripepi R, Torino C, Garozzo M, Battaglia GG, Marcantoni C, Infantone L, Giordano G, De Giorgi ML, Lupia M, Bruzzese V, Zoccali C

Abstract
BACKGROUND: Chest ultrasound (US) is a non-invasive well-validated technique for estimating extravascular lung water (LW) in patients with heart diseases and in end-stage renal disease. We systematically applied this technique to the whole peritoneal dialysis (PD) population of five dialysis units.
METHODS: We studied the cross-sectional association between LW, echocardiographic parameters, clinical [pedal oedema, New York Heart Association (NYHA) class] and bioelectrical impedance analysis (BIA) markers of volume status in 88 PD patients.
RESULTS: Moderate to severe lung congestion was evident in 41 (46%) patients. Ejection fraction was the echocardiographic parameter with the strongest independent association with LW (r = -0.40 P = 0.002). Oedema did not associate with LW on univariate and multivariate analysis. NYHA class was slightly associated with LW (r = 0.21 P = 0.05). Among patients with severe lung congestion, only 27% had pedal oedema and the majority (57%) had no dyspnoea (NYHA Class I). Similarly, the prevalence of patients with BIA, evidence of volume excess was small (11%) and not significantly different (P = 0.79) from that observed in patients with mild or no congestion (9%).
CONCLUSIONS: In PD patients, LW by chest US reveals moderate to severe lung congestion in a significant proportion of asymptomatic patients. Intervention studies are necessary to prove the usefulness of chest US for optimizing the control of fluid excess in PD patients.

PMID: 22573237 [PubMed - indexed for MEDLINE]

Chronic kidney disease is not associated with a higher risk for mortality or acute kidney injury in transcatheter aortic valve implantation.

Tue, 07/09/2013 - 10:26
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Chronic kidney disease is not associated with a higher risk for mortality or acute kidney injury in transcatheter aortic valve implantation.

Nephrol Dial Transplant. 2012 Sep;27(9):3502-8

Authors: Wessely M, Rau S, Lange P, Kehl K, Renz V, Schönermarck U, Steinbeck G, Fischereder M, Boekstegers P

Abstract
BACKGROUND: Transcatheter aortic valve implantation (TAVI) has emerged as a new therapeutic option for surgical high-risk patients with severe aortic stenosis (AS). Many of these patients suffer from chronic kidney disease (CKD), which substantially increases the risk for acute kidney injury (AKI), need for renal replacement therapy (RRT) and mortality after surgical aortic valve repair. The impact of pre-existing CKD for the outcome of TAVI is still unclear.
METHODS: We retrospectively evaluated 199 consecutive patients with symptomatic high-grade AS undergoing TAVI with the CoreValve prosthesis at our centre. We analysed incidence and predictive factors for AKI, RRT and mortality in patients with and without CKD (defined as an estimated glomerular filtration rate <60 mL/min).
RESULTS: 26.8% of the patients suffered from AKI, 4.9% needed RRT and 5.5% died. All patients on chronic haemodialysis (n = 10) survived. There were no significant differences between patients with or without CKD concerning the incidence of AKI, RRT and mortality. Age, peripheral vascular disease and the need for blood transfusion were independently associated with AKI. AKI proved to be a predictive factor for mortality.
CONCLUSIONS: Transcatheter aortic valve replacement with the CoreValve prosthesis does not seem to bear an increased risk for patients with CKD. For surgical high-risk patients with severe AS, a more liberal consideration for TAVI as an alternative to open surgery might be justified.

PMID: 22535634 [PubMed - indexed for MEDLINE]

VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.

Tue, 07/09/2013 - 10:26
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VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey.

Nephrol Dial Transplant. 2012 Sep;27(9):3588-94

Authors: Cozzolino M, Brancaccio D, Cannella G, Messa P, Gesualdo L, Marangella M, LoDeserto C, Pozzato M, Rombolà G, Costanzo AM, di Luzio Paparatti U, Mazzaferro S, FARO Study Group

Abstract
BACKGROUND: Chronic kidney disease (CKD) patients affected by mineral bone disorders (MBD) have higher rates of all-cause and cardiovascular-related mortality. Approximately, one-third of dialysis patients have low serum parathyroid hormone (PTH) levels (≤ 150 pg/mL). However, the reason why these patients have higher mortality compared to patients with normal PTH levels has not yet been fully elucidated.
METHODS: The FARO study was performed on 2453 Italian patients followed prospectively from 28 dialysis centres over a 2-year period. Data were collected every 6 months and end points included time-to-death cumulative probability in patients with serum intact PTH (iPTH) ≤ 150 pg/mL and the effect of vitamin D receptor activation (VDRA) therapy. Kaplan-Meier curves and proportional hazards regression models stratified by PTH levels (i.e. ≤ 150 and >150 pg/mL) were used to determine cumulative probability of time-to-death and adjusted hazard ratios (HRs) for demographic, clinical and CKD-MBD treatment characteristics.
RESULTS: The cumulative probability of death was higher (P < 0.01) for patients with serum iPTH levels ≤ 150 pg/mL [25.1%, 95% confidence interval (CI): 22.1-28.5 at 18 months] versus those with serum iPTH levels within the normal range (18.0%, 95% CI: 16.1-20.1). In a model with time-dependent covariates restricted to time periods when patients had iPTH levels ≤ 150 pg/mL, lower mortality was observed in patients treated with VDRA [i.e. HR = 0.62, 95% CI: 0.42-0.92 for oral or intravenous (IV) calcitriol; HR = 0.18, 95% CI: 0.04-0.8 for IV paricalcitol] versus those not receiving any VDRA (P < 0.01) independently of other variables. Patients who received IV paricalcitol, compared with either oral or IV calcitriol, showed reduced mortality, but this was not statistically significant (HR = 0.3, 95% CI: 0.07-1.31, P = 0.11).
CONCLUSION: Results from this observational study suggest that VDRA therapy was associated with improved survival in dialysis patients, even with low serum iPTH levels.

PMID: 22523119 [PubMed - indexed for MEDLINE]

Chronic renal denervation increases renal tubular response to P2X receptor agonists in rats: implication for renal sympathetic nerve ablation.

Tue, 07/09/2013 - 10:26
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Chronic renal denervation increases renal tubular response to P2X receptor agonists in rats: implication for renal sympathetic nerve ablation.

Nephrol Dial Transplant. 2012 Sep;27(9):3443-8

Authors: Kowalski R, Kreft E, Kasztan M, Jankowski M, Szczepanska-Konkel M

Abstract
BACKGROUND: Kidney noradrenergic innervation regulates tubular function. Adenosine triphosphate (ATP)-a co-transmitter of norepinephrine-acts on purinoceptors, including ion channel receptor, P2X. P2X receptor agonists, α,β-methylene ATP (α,β-meATP) and β,γ-methylene ATP (β,γ-meATP), induce natriuresis. Regarding the functional co-localization of adrenoceptors and P2X receptors, we evaluated rat renal tubular system sensitivity to natriuretic action of P2X receptor agonists in chronically denervated kidney.
METHODS: Clearance studies with α,β-meATP and β,γ-meATP (intravenous infusion rate, 2 µmol/kg + 20 nmol/kg/min) were performed after bilateral surgical kidney denervation (DNx) and sham-operation (Sham). Na/K-ATPase activity was measured in isolated rat renal proximal tubules.
RESULTS: In DNx compared with Sham, saline infusion significantly increased renal sodium and urine excretion and P2X receptor agonist infusion was significantly more natriuretic and diuretic. In DNx and Sham, respectively, α,β-meATP increased fractional excretion of sodium (FE(Na)) by 2 ± 0.3 and 0.6 ± 0.1% and urine (FE(V)) by 1.6 ± 0.3 and 0.9 ± 0.2%; β,γ-meATP had similar effects. In both groups of rats, natriuretic and diuretic actions were abolished by P2 receptor blocker (pyridoxal-phosphate-6-azophenyl-2',4'-disulphonate, PPADS), mean arterial blood pressure and glomerular filtration rate remained unchanged during infusion of P2X receptor agonists and antagonist and basal Na/K-ATPase activities in isolated proximal tubules were similar. Both α,β-meATP and β,γ-me-ATP decreased the Na/K-ATPase activity, with 20% inhibition (P < 0.05) in denervated and innervated rats; these inhibitory effects were abolished in the presence of PPADS.
CONCLUSIONS: Decreased renal sympathetic activity enhances the natriuretic effect of P2X receptor stimulation. This effect is probably not related to altered Na/K-ATPase activity in renal proximal tubules.

PMID: 22516625 [PubMed - indexed for MEDLINE]

Anti-microbial locks increase the prevalence of Staphylococcus aureus and antibiotic-resistant Enterobacter: observational retrospective cohort study.

Tue, 07/09/2013 - 10:26
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Anti-microbial locks increase the prevalence of Staphylococcus aureus and antibiotic-resistant Enterobacter: observational retrospective cohort study.

Nephrol Dial Transplant. 2012 Sep;27(9):3575-81

Authors: Dixon JJ, Steele M, Makanjuola AD

Abstract
BACKGROUND: Anti-microbial lock solutions (AML), in conjunction with systemic antibiotics, may successfully treat tunnelled haemodialysis catheter-related bloodstream infections (CR-BSI). It is unknown whether AML promote anti-microbial resistance.
METHODS: This is a retrospective cohort study of all CR-BSI (2003-2006) in our dialysis unit. Controls (n = 265) were treated with systemic vancomycin and gentamicin. In addition to the systemic antibiotics, the study group (n = 662) received AML containing vancomycin and gentamicin during inter-dialytic periods. Antibiotic sensitivity/resistance profiles of all organisms were analysed. Changes in the incidence of infection (chi-square test) and resistant organisms (Fisher's exact test) were calculated.
RESULTS: The incidence of CR-BSI decreased from 8.50/1000 catheter days (controls) to 3.80 (study group; P < 0.0001), and the incidence of relapses decreased (P = 0.0027). The number needed to treat to prevent subsequent bacteraemia using an AML adjunct is 3 ± 0.4. The proportion of Gram-positive cultures increased (P < 0.0001), including Staphylococcus aureus (P = 0.03), but the proportion of methicillin-resistant S. aureus (P = 0.87) and vancomycin resistance (P = 0.90) did not. Increased gentamicin resistance (P < 0.0001) and ciprofloxacin resistance (P = 0.04) were observed in Gram-negative cultures. Gentamicin resistance [relative risk (RR) > 15.29; P < 0.0001] and ciprofloxacin resistance (RR = 6; P = 0.007) increased in Enterobacter species, but not Pseudomonas or Escherichia coli species.
CONCLUSION: AML decrease CR-BSI incidence, although proportions of S. aureus and anti-microbial-resistant Enterobacter are increased.

PMID: 22513704 [PubMed - indexed for MEDLINE]

Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

Tue, 07/09/2013 - 10:26
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Prostate specific antigen levels and prostate cancer detection rates in patients with end stage renal disease.

J Urol. 2012 Jun;187(6):2061-5

Authors: Chen CJ, Heldt JP, Anderson KM, Ruckle HC, Agarwal G, Smith DL, Schlaifer AE, Richards GD, Arnold DC, Baldwin DD

Abstract
PURPOSE: Patients with end stage renal disease plus prostate cancer are ineligible to receive a renal transplant at most centers until an acceptable cancer-free period is demonstrated. To our knowledge previously established prostate specific antigen reference ranges have not been validated in patients with end stage renal disease. We determined age stratified 95th percentile prostate specific antigen reference ranges and the prostate cancer detection rate at specific prostate specific antigen intervals for patients with end stage renal disease.
MATERIALS AND METHODS: We retrospectively reviewed the records of 775 male patients with end stage renal disease on the waiting list for a renal transplant who had undergone a serum prostate specific antigen test. Prostate specific antigen was stratified by age at the time of the blood test and 95th percentile reference ranges were calculated for each decade. A total of 80 patients underwent prostate biopsy for increased prostate specific antigen and/or abnormal digital rectal examination. The cancer detection rate was calculated for specific prostate specific antigen reference ranges.
RESULTS: The age specific 95th percentile prostate specific antigen references ranges were 0 to 4.0 ng/ml for ages 40 to 49 in 137 patients, 0 to 5.3 ng/ml for ages 50 to 59 in 257, 0 to 10.5 ng/ml for ages 60 to 69 in 265 and 0 to 16.6 ng/ml for ages 70 to 79 years in 69. The cancer detection rate was 44%, 38% and 67% for prostate specific antigen 2.5 to 4.0, 4 to 10 and greater than 10 ng/ml, respectively.
CONCLUSIONS: In our study population of patients with end stage renal disease age stratified prostate specific antigen was higher than in the general population. The cancer detection rate was increased in our patients with end stage renal disease compared to that in patients with normal renal function at specific prostate specific antigen intervals. Lower prostate specific antigen cutoffs may be appropriate to recommend prostate biopsy in patients with end stage renal disease.

PMID: 22498219 [PubMed - indexed for MEDLINE]

Endothelial cell transforming growth factor-β receptor activation causes tacrolimus-induced renal arteriolar hyalinosis.

Tue, 07/09/2013 - 10:26
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Endothelial cell transforming growth factor-β receptor activation causes tacrolimus-induced renal arteriolar hyalinosis.

Kidney Int. 2012 Oct;82(8):857-66

Authors: Chiasson VL, Jones KA, Kopriva SE, Mahajan A, Young KJ, Mitchell BM

Abstract
Arteriolar hyalinosis is a common histological finding in renal transplant recipients treated with the calcineurin inhibitor tacrolimus; however, the pathophysiologic mechanisms remain unknown. In addition to increasing transforming growth factor (TGF)-β levels, tacrolimus inhibits calcineurin by binding to FK506-binding protein 12 (FKBP12). FKBP12 alone also inhibits TGF-β receptor activation. Here we tested whether tacrolimus binding to FKBP12 removes an inhibition of the TGF-β receptor, allowing ligand binding, ultimately leading to receptor activation and arteriolar hyalinosis. We found that specific deletion of FKBP12 from endothelial cells was sufficient to activate endothelial TGF-β receptors and induce renal arteriolar hyalinosis in these knockout mice, similar to that induced by tacrolimus. Tacrolimus-treated and knockout mice exhibited significantly increased levels of aortic TGF-β receptor activation as evidenced by SMAD2/3 phosphorylation, along with increased collagen and fibronectin expression compared to controls. Treatment of isolated mouse aortas with tacrolimus increased TGF-β receptor activation and collagen and fibronectin expression. These effects were independent of calcineurin, absent in endothelial denuded aortic rings, and could be prevented by the small molecule TGF-β receptor inhibitor SB-505124. Thus, endothelial cell TGF-β receptor activation is sufficient to cause vascular remodeling and renal arteriolar hyalinosis.

PMID: 22495293 [PubMed - indexed for MEDLINE]

Is Cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies?

Tue, 07/09/2013 - 10:26
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Is Cystatin C a promising marker of renal function, at birth, in neonates prenatally diagnosed with congenital kidney anomalies?

Nephrol Dial Transplant. 2012 Sep;27(9):3477-82

Authors: Parvex P, Combescure C, Rodriguez M, Girardin E

Abstract
BACKGROUND: Despite the increased prenatal diagnosis of congenital abnormalities of the kidney and urinary tract (CAKUT), no reliable renal marker for glomerular filtration rate (GFR) has been validated yet in neonates. Cystatin C (CysC) is specific to the neonate and is proposed as a sensitive marker for this population. The aims of the study were first to define a reference interval in our center of CysC at birth in normal term babies and assess CysC as a marker of GFR in a group of term neonates prenatally diagnosed with CAKUT compared to controls.
METHODS: One hundred normal term neonates (control group) and 33 neonates with kidney malformation (KM) had the CysC levels in their cord blood measured. A reference interval for CysC in controls was calculated using non-parametric methods. CysC from controls was compared first to the whole group of neonates with KM, then with KM group divided in infants (n = 20) with unilateral kidney malformation (UKM) and those (n = 13) with bilateral kidney malformation (BKM). A multivariable analysis was performed to assess the difference in CysC between the groups with adjustment on other factors. The ability of CysC to discriminate neonates with BKM from the controls was assessed by a non-parametric receiver-operated characteristics (ROC) curve.
RESULTS: In the control group, the CysC reference interval was [1.54-2.64] mg/L with a median (M) CysC of 2.02 IQR [1.86-2.23]. In the neonates with KM, M CysC was 1.98 IQR [1.79-2.34]; 1.88 IQR [1.76-2.01] in the UKM group and 2.52 IQR [2.16-2.71] in BKM group. Using a multivariate regression analyses, CysC was significantly increased (P < 0.001) in BKM compared to controls with an increment of CysC of 24.5%, and independent from gender, weight and size. The ROC curve analyses, comparing BKM versus controls with a chosen cut-off for CysC of 2.34, showed a sensitivity of 69% and a specificity of 86%.
CONCLUSIONS: Comparing CysC with a reference interval of CysC validated in our center, we showed a significant increase of CysC in neonates presenting BKM compared to controls and those with UKM.

PMID: 22474211 [PubMed - indexed for MEDLINE]

Dialysis in public and private hospitals in Queensland.

Tue, 07/09/2013 - 10:26
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Dialysis in public and private hospitals in Queensland.

Intern Med J. 2012 Aug;42(8):887-93

Authors: Gray NA, Dent H, McDonald SP

Abstract
BACKGROUND: Clinical outcomes for patients treated in public and private hospitals may be different.
AIM: The aim of the study was to compare the characteristics and outcomes of patients receiving dialysis at public and private hospitals in Queensland.
METHODS: Incident adult dialysis patients in Queensland registered with the Australia and New Zealand Dialysis and Transplant Registry between 1999 and 2009 were classified by dialysis modality at either a public or private hospital. Outcomes were dialysis patient characteristics and survival.
RESULTS: Three thousand, three hundred and ten patients commenced dialysis in public hospitals, 1939 haemodialysis (HD) and 1371 peritoneal dialysis (PD). Seven hundred and ninety-three patients commenced dialysis in private hospitals, 757 HD and 36 PD. Compared with public HD, private HD patients were older, had more coronary artery disease and less diabetes, and were more likely to live in an urban area. Public HD patients were more likely to be obese and referred late to a nephrologist. Nearly all indigenous patients were managed in public hospitals. Private patients were more likely to have an arteriovenous fistula or graft at first HD (P < 0.001) but not after excluding late referrals (P = 0.09). Public hospitals provided longer HD sessions and more HD hours per week for all age groups except 75+ years. Compared with public hospital HD, patient survival adjusted for multiple variables was comparable for private hospital HD (hazard ratio 1.20 (95% confidence interval 0.98-1.46, P = 0.07)) but worse for public PD (hazard ratio 1.14 (95% confidence interval 1.05-1.24, P = 0.002)).
CONCLUSION: Private HD patients are older and less likely to be diabetic than public patients. Patient survival is worse for public PD than public HD.

PMID: 22472068 [PubMed - indexed for MEDLINE]

Outbreaks of Pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of Pneumocystis: implications for transmission and virulence.

Tue, 07/09/2013 - 10:26
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Outbreaks of Pneumocystis pneumonia in 2 renal transplant centers linked to a single strain of Pneumocystis: implications for transmission and virulence.

Clin Infect Dis. 2012 May;54(10):1437-44

Authors: Sassi M, Ripamonti C, Mueller NJ, Yazaki H, Kutty G, Ma L, Huber C, Gogineni E, Oka S, Goto N, Fehr T, Gianella S, Konrad R, Sing A, Kovacs JA

Abstract
BACKGROUND: There have been numerous reports of clustered outbreaks of Pneumocystis pneumonia (PCP) at renal transplant centers over the past 2 decades. It has been unclear whether these outbreaks were linked epidemiologically to 1 or several unique strains, which could have implications for transmission patterns or strain virulence.
METHODS: Restriction fragment length polymorphism (RFLP) analysis was used to compare Pneumocystis isolates from 3 outbreaks of PCP in renal transplant patients in Germany, Switzerland, and Japan, as well as nontransplant isolates from both human immunodeficiency virus (HIV)-infected and uninfected patients.
RESULTS: Based on RFLP analysis, a single Pneumocystis strain caused pneumonia in transplant patients in Switzerland (7 patients) and Germany (14 patients). This strain was different from the strain that caused an outbreak in transplant patients in Japan, as well as strains causing sporadic cases of PCP in nontransplant patients with or without HIV infection.
CONCLUSIONS: Two geographically distinct clusters of PCP in Europe were due to a single strain of Pneumocystis. This suggests either enhanced virulence of this strain in transplant patients or a common, but unidentified, source of transmission. Outbreaks of PCP can be better understood by enhanced knowledge of transmission patterns and strain variation.

PMID: 22431811 [PubMed - indexed for MEDLINE]

Linking Pneumocystis epidemiology, transmission, and virulence.

Tue, 07/09/2013 - 10:26
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Linking Pneumocystis epidemiology, transmission, and virulence.

Clin Infect Dis. 2012 May;54(10):1445-7

Authors: de Boer MG

PMID: 22431810 [PubMed - indexed for MEDLINE]

Complications after use of gastric segments for lower urinary tract reconstruction.

Tue, 07/09/2013 - 10:26
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Complications after use of gastric segments for lower urinary tract reconstruction.

J Urol. 2012 May;187(5):1823-7

Authors: Castellan M, Gosalbez R, Bar-Yosef Y, Labbie A

Abstract
PURPOSE: We retrospectively reviewed our experience with the use of gastric segments for lower urinary tract reconstruction with an emphasis on long-term complications.
MATERIALS AND METHODS: A total of 29 patients underwent reconstruction of the lower urinary tract using gastric segments between 1993 and 2000. Diagnoses included neurogenic bladder (21), cloacal exstrophy (5), solitary kidney/ectopic ureter (1), posterior urethral valves (1) and rhabdomyosarcoma of prostate (1). Gastric segment was used as gastrocystoplasty (21), composite gastroenteric cystoplasty (6), demucosalized gastrocystoplasty (1) and continent gastric reservoir (1).
RESULTS: Mean followup was 13.9 years (range 9 to 16.5). Complications were seen in 15 (51.7%) patients. Seven patients had the hematuria-dysuria syndrome, which was intractable in 1 and necessitated excision of the gastric patch. Due to severe complications necessitating major reoperations 3 patients underwent re-augmentation with enteric segments without excision of the gastric tissue (composite). One patient who underwent demucosalized gastrocystoplasty had excision of the gastric tissue and re-augmentation with enteric segment due to contraction of the gastric patch. A stone developed in 1 patient with a composite gastroenteric reservoir. Malignancy developed in the reservoir in 3 patients 11, 12 and 14 years after gastrocystoplasty, and all 3 died of metastasis.
CONCLUSIONS: We do not recommend the use of gastric segments for reconstruction of the lower urinary tract due to the high incidence of reoperations and complications. In patients in whom gastric segments were used in the past for lower urinary tract reconstruction, regular surveillance and close followup are strongly advocated.

PMID: 22425048 [PubMed - indexed for MEDLINE]

Survival comparisons between haemodialysis and peritoneal dialysis.

Tue, 07/09/2013 - 10:26
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Survival comparisons between haemodialysis and peritoneal dialysis.

Nephrol Dial Transplant. 2012 Sep;27(9):3385-7

Authors: Noordzij M, Jager KJ

PMID: 22399492 [PubMed - indexed for MEDLINE]

Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.

Tue, 07/09/2013 - 10:26
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Arteriolar vascular smooth muscle cell differentiation in benign nephrosclerosis.

Nephrol Dial Transplant. 2012 Sep;27(9):3493-501

Authors: Bockmeyer CL, Kern DS, Forstmeier V, Lovric S, Modde F, Agustian PA, Steffens S, Birschmann I, Traeder J, Dämmrich ME, Schwarz A, Kreipe HH, Bröcker V, Becker JU

Abstract
BACKGROUND: Benign nephrosclerosis (bN) is the most prevalent form of hypertensive damage in kidney biopsies. It is defined by early hyalinosis and later fibrosis of renal arterioles. Despite its high prevalence, very little is known about the contribution of arteriolar vascular smooth muscle cells (VSMCs) to bN. We examined classical and novel candidate markers of the normal contractile and the pro-fibrotic secretory phenotype of VSMCs in arterioles in bN.
METHODS: Sixty-three renal tissue specimens with bN and eight control specimens were examined by immunohistochemistry for the contractile markers caldesmon, alpha-smooth muscle actin (alpha-SMA), JunB, smoothelin and the secretory marker S100A4 and by double stains for caldesmon or smoothelin with S100A4.
RESULTS: Smoothelin immunostaining showed an inverse correlation with hyalinosis and fibrosis scores, while S100A4 correlated with fibrosis scores only. Neither caldesmon, alpha-SMA nor JunB correlated with hyalinosis or fibrosis scores. Cells in the arteriolar wall were exclusively positive either for caldesmon/smoothelin or S100A4.
CONCLUSIONS: This is the first systematic analysis of VSMC differentiation in bN. The results suggest that smoothelin is the most sensitive marker for the contractile phenotype and that S100A4 could be a novel marker for the secretory phenotype in vivo. The other markers did not seem to differentiate these phenotypes in bN. Thus, VSMC phenotype markers should be defined in the context of the vessel segment and disease under examination. S100A4 could not only be a marker of pro-fibrotic secretory VSMCs in bN but also an important mediator of arteriolar fibrosis.

PMID: 22319217 [PubMed - indexed for MEDLINE]

Modulation of 11β-hydroxysteroid dehydrogenase 1 by β2-adrenoceptor in the ischaemia-reperfused rat kidney.

Tue, 07/09/2013 - 10:26
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Modulation of 11β-hydroxysteroid dehydrogenase 1 by β2-adrenoceptor in the ischaemia-reperfused rat kidney.

Nephrol Dial Transplant. 2012 Sep;27(9):3456-64

Authors: Nakamura A, Miyagawa M, Yanagawa Y

Abstract
BACKGROUND: 11β-Hydroxysteroid dehydrogenase Type 1 (11βHSD-1) amplifies intracellular levels of active glucocorticoids which possess protective effects against organ ischaemia and reperfusion (I/R). However, the mechanisms by which 11βHSD-1 is modified after a renal I/R challenge remain unclear. This study investigated the effect of β(2)-adrenoceptor (β(2)-AR) activation and the subsequent signalling pathways on renal 11βHSD-1 gene expression following renal I/R.
METHODS: Renal I/R was induced using 25 min of bilateral renal artery occlusion in 4-week-old Wistar rats followed by an intraperitoneal injection of various doses of adeno-β(2)-AR gene. Following renal I/R, kidneys, plasma and urine were collected to assay 11βHSD messenger RNA (mRNA) levels, β(2)-AR signalling cascades and renal function.
RESULTS: On the second day after the renal I/R challenge, there was a reduction in renal 11βHSD-1 mRNA levels associated with a decrease in stimulatory G protein α (Gsα) and adenylate cyclase-1 (ACY-1) in the kidney. The addition of the adeno-β(2)-AR gene resulted in greater increases in 11βHSD-1 mRNA and β(2)-AR-Gsα-ACY-cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) activity in the kidney but had no effect on 11βHSD-2 mRNA or protein kinase C levels in the kidney.
CONCLUSIONS: Over-expression of β(2)-AR resulting from the gene delivery improved renal function and 11βHSD-1 production following renal I/R, which were actions exerted through the cAMP-PKA pathway. The stimulatory effect of functional β(2)-AR activation on renal 11βHSD-1 expression may offer a means of protection from renal I/R injury.

PMID: 22187316 [PubMed - indexed for MEDLINE]

Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease.

Tue, 07/09/2013 - 10:26
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Prevalence and prognosis of unrecognized myocardial infarctions in chronic kidney disease.

Nephrol Dial Transplant. 2012 Sep;27(9):3482-8

Authors: Rizk DV, Gutierrez O, Levitan EB, McClellan WM, Safford M, Soliman EZ, Warnock DG, Muntner P

Abstract
BACKGROUND: Unrecognized myocardial infarctions (UMIs) are common in the general population but have not been well studied in patients with chronic kidney disease (CKD). The purpose of this study was to determine the prevalence and prognosis for mortality of UMI among adults with CKD.
METHODS: The current study included 18 864 participants in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study who completed a baseline examination including a 12-lead electrocardiogram (ECG). UMI was defined as the presence of myocardial infarction (MI) by Minnesota ECG classification in the absence of self-reported or recognized MI (RMI). Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation and albuminuria using albumin-to-creatinine ratio from a spot urine sample. All-cause mortality was assessed over a median 4 years of follow-up.
RESULTS: The prevalence of UMI was 4, 6, 6 and 13% among participants with eGFR levels of ≥ 60, 45-59.9, 30-44.9 and <30 mL/min/1.73 m(2), respectively, and 4, 5, 7 and 10% among participants with albuminuria levels of <10, 10-29.9, 30-299.9 and ≥ 300 mg/g, respectively. Compared to those with no MI, the multivariable adjusted hazard ratio for all-cause mortality associated with UMI and RMI was 1.65 [95% confidence interval (CI): 1.09-2.49] and 1.65 (95% CI: 1.20-2.26), respectively, among individuals with an eGFR <60 mL/min/1.73 m(2) and 1.49 (95% CI: 1.03-2.16) and 1.88 (95% CI: 1.40-2.52) among individuals with albuminuria ≥ 30 mg/g. Conclusion UMIs are common among individuals with an eGFR <60 mL/min/1.73 m(2) and albuminuria and associated with an increased mortality risk.

PMID: 22167594 [PubMed - indexed for MEDLINE]

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