Publicações - 2006

Efficacy of lipid lowering drug treatment for diabetic and non-diabetic patients: meta-analysis of randomised controlled trials

João Costa 1, Margarida Borges 1, Cláudio David 2, António Vaz Carneiro 1*

1 Center for Evidence-Based Medicine, University of Lisbon School of Medicine, Lisbon, Portugal
2 Department of Cardiology, Santa Maria University Hospital, Lisbon

* Correspondence to:

BMJ 2006; 332(7550): 1115-24

To evaluate the clinical benefit of lipid lowering drug treatment in patients with and without diabetes mellitus, for primary and secondary prevention.

Systematic review and meta-analysis.

Data sources
Cochrane, Medline, Embase, and reference lists up to April 2004.

Study selection
Randomised, placebo controlled, double blind trials with a follow-up of at least three years that evaluated lipid lowering drug treatment in patients with and without diabetes mellitus.

Data extraction
Two independent reviewers extracted data. The primary outcome was major coronary events defined as coronary heart disease death, non-fatal myocardial infarction, or myocardial revascularisation procedures.

Twelve studies were included. Lipid lowering drug treatment was found to be at least as effective in diabetic patients as in non-diabetic patients. In primary prevention, the risk reduction for major coronary events was 21% (95% confidence interval 11% to 30%; P<0.0001) in diabetic patients and 23% (12% to 33%; P=0.0003) in non-diabetic patients. In secondary prevention, the corresponding risk reductions were 21% (10% to 31%; P=0.0005) and 23% (19% to 26%; P0.00001). However, the absolute risk difference was three times higher in secondary prevention. When results were adjusted for baseline risk, diabetic patients benefited more in both primary and secondary prevention. Blood lipids were reduced to a similar degree in both groups.

The evidence that lipid lowering drug treatment (especially statins) significantly reduce cardiovascular risk in diabetic and non-diabetic patients is strong and suggests that diabetic patients benefit more, in both primary and secondary prevention. Future research should define the threshold for treatment of these patients and the desired target lipid concentrations, especially for primary prevention.

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Peritoneal fast transport in incident peritoneal dialysis patients is not consistently associated with systemic inflammation

Rodrigues AS, Almeida M, Fonseca I, Martins M, Carvalho MJ, Silva F, Correia C, Santos MJ, Cabrita A.

Nephrology Department, Hospital Geral de Santo Antonio, Porto, Portugal.

Nephrol Dial Transplant. 2006; 21(3): 763-9

BACKGROUND: The determinants of peritoneal fast transport status at the beginning of peritoneal dialysis (PD) are still under debate. The relationship between fast transport status and inflammation or co-morbidity, and its impact on patient survival are not fully elucidated. Our objective was to investigate if fast transport status in incident patients is associated with markers of inflammation and atherosclerosis, and its relationship to patient survival. METHODS: Seventy-three incident patients on PD performed a 3.86% peritoneal equilibrium test (PET) at 4.7+/-2.7 months after starting PD. Doppler carotid wall intima-media thickness (IMT) and the presence of carotid plaque wereused as markers of atherosclerosis. C-reactive protein (CRP) and serum interleukin-6 (IL-6) were evaluated as markers of systemic inflammation. Baseline plasma levels of albumin, homocysteine, lipoprotein (a) [Lp(a)] and other lipid parameters were measured. Body mass index and residual renal function (RRF) were calculated. Patients were classified with the Davies co-morbidity score.

RESULTS: The dialysate-plasma creatinine ratio (D/P creatinine) was 0.75+/-0.10; 26% were fast transporters (D/P >/=0.85). In comparison with other transport categories, these had similar age, body mass index and RRF, and did not present a higher co-morbidity score than non-fast transporters. IMT did not significantly differ between groups. By multiple regression analysis, baseline peritoneal small solute transport was not related to systemic inflammation biomarkers. Fast transporters did not present higher levels of CRP or serum IL-6. Plasma levels of lipids, Lp(a), calcium x phosphorus product and albumin also did not differ between groups. Similar results were obtained when patients were grouped according to mass transfer area coefficient for creatinine. Patients with more than two co-morbidities had lower levels of plasma albumin (3.6+/-0.58 vs 3.9+/-0.9 g/dl, P = 0.054), significantly higher median levels of serum IL-6 (19.3 vs 9.2 pg/ml, P = 0.003) and wider IMT (0.90+/-0.36 vs 0.65+/-0.28 mm, P = 0.017). Multivariate analysis confirmed that baseline peritoneal transport was not a significant determinant of patient survival (P = 0.848), while the co-morbidity score remained significant (hazard ratio = 3.48, 95% confidence interval = 1.29-9.38, P = 0.014).

CONCLUSION: Initial fast transport was not associated with systemic inflammation and atherosclerosis. In a population with preserved RRF and absence of baseline serious co-morbidity, it was not predictive of worse prognosis. Other determinants of early peritoneal fast transport deserve investigation.

PMID: 16332703 [PubMed - as supplied by publisher]

Long-term peritoneal dialysis experience in Portugal

A.S. Rodrigues 1, C.B. Matos 1, F. Silva 1, I. Fonseca 1, C. Nogueira 2, J. Santos 2, A.S. Silva 2, A. Cabrita 1

1 Department of Nephrology, Hospital Geral Santo Antonio, Porto - Portugal
2 Department of Surgery, Hospital Geral Santo Antonio, Porto - Portugal

The International Journal of Artificial Organs 2006; 29 (12): 00-00

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Anaemia correction in predialysis elderly patients: influence of the antihypertensive therapy on darbepoietin dose

Neves PL, Baptista A, Morgado E, Iglesias A, Carrasqueira H, Faisca M, Soares C, Silva AP.

Servico de Nefrologia, Hospital Distrital de Faro, Rua Leao Penedo, 8000, Faro, Portugal,

Int Urol Nephrol. 2006 Sep 26; [Epub ahead of print]

Anaemia and hypertension are common in patients with chronic renal insufficiency. The correction of anaemia with erythropoiesis stimulating agents (ESA) can improve survival and decrease the decline of renal function. Angiotensin converting-enzyme inhibitors (ACEI) and angiotensin II receptor blockers (AIIRA) can also slow the progression of renal failure, but the blockade of the renin-angiotensin system can worsen anaemia. The aim of our study was to assess the impact of antihypertensive therapy (ACEI plus AIIRA) in the requirements of darbepoietin in a group of elderly predialysis patients. We included 71 patients (m = 39, f = 32), mean age of 76.3 years with a mean creatinine clearance of 17.5 ml/min. Patients were divided in two groups according to their antihypertensive therapy: G-I patients under ACEI or AIIRA therapy and G-II normotensive patients or hypertensive patients under antihypertensive drugs other than ACEI or AIIRA. The groups were compared regarding demographic, nutritional, biochemical and inflammatory parameters. We also compared the mean darbepoietin dose. In GI the mean dose of darbepoietin was higher than in GII (0.543 vs. 0.325 microg/kg/week, P = 0.032). We did not find any difference regarding other parameters analysed. We conclude that ACEI and AIIRA can increase the needs of darbepoietin in predialysis elderly patients. However, when formally indicated to treat hypertension in a specific patient, they should not be switched to another antihypertensive agent. Instead, in such cases, higher doses of ESA should be used, if necessary.

PMID: 17001498 [PubMed - as supplied by publisher]

Nutritional and inflammatory status influence darbepoetin dose in pre-dialysis elderly patients

Neves PL, Morgado E, Faisca M, Carrasqueira H, Baptista A, Silva AP.

Servico de Nefrologia, Hospital Distrital de Faro, Rua Leao Penedo, 8000, Faro, Portugal,

Int Urol Nephrol. 2006 Dec 7; [Epub ahead of print]

Anaemia is a common finding in elderly patients particularly in those with chronic kidney disease. Effective correction of anaemia improves survival and quality of life. The association between anaemia and a poor nutritional status as well as the presence of inflammation has already been documented. The aim of our study was to assess the impact of the nutritional and inflammatory status on darbepoetin dose requirements of elderly patients followed in a "Chronic Kidney Disease" outpatient clinic. We included 71 elderly patients (age >/= 65 years) in a "Chronic Kidney Disease" outpatient clinic. Creatinine Clearance (CrCl) was estimated according to the Cockroft-Gault equation. Nutritional status was evaluated by biochemical and anthropometric parameters. Tumour Necrosis Factor-alpha (TNF-alpha), Interleukin-6 (IL-6) and high sensitivity C-reactive protein (hs-CRP) were used as biomarkers of inflammation. Our patients (56% males) with a mean age of 76.2 +/- 6.6 years were followed for 33.1 +/- 43.6 months. Mean eCrCl was 13.5 +/- 7.2 ml/mn/1.73 m(2). All patients were under supplemental iron therapy and 74.7% needed darbepoietin (0.762 +/- 0.6 (mug/kg/week) to correct anaemia. Among the several variables regressed on darbepoietin dose, in a multiple regression model, only Hb, IL-6 and TNF-alpha levels and SGA score predicted the need for higher doses of darbepoietin. (r = 0.677; r (2) = 0.459). In Conclusion, in our pre-dialysis elderly patients, markers of a poor nutritional status (SGA and albumin) and inflammation (IL-6 and TNF-alpha) independently predicted the use of higher doses of darbepoietin to correct anaemia.

PMID: 17160447 [PubMed - as supplied by publisher]

Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting

J Calado (1), J Loeffler (2), O Sakallioglu (3), F Gok (3), K Lhotta (2), J Barata (4) and J Rueff (1)

(1) Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Lisbon, Portugal, (2) Division of Nephrology, Innsbruck Medical University, Innsbruck, Austria (3) Division of Pediatric Nephrology, GATA Medical Faculty, Ankara, Turkey (4) Department of Nephrology, Hospital de Santa Cruz, Lisbon, Portugal

Kidney International 2006; 69: 852-855


Familial renal glucosuria (FRG) is an inherited renal tubular disorder characterized by persistent isolated glucosuria in the absence of hyperglycemia. Mutations in the sodium/glucose co-transporter SGLT2 coding gene, SLC5A2, were recently found to be responsible for the disorder. Here, we report the molecular and phenotype study of five unrelated FRG families. Five patients were identified and their family members screened for glucosuria. SLC5A2 coding region of index cases was polymerase chain reaction amplified and sequenced. Five different mutations are reported, including four novel alleles. The IVS12+1G>A and p.A102V alleles were identified in homozygosity in index patients of two unrelated families. A proband from another family was compound heterozygous for the p.R132H and p.A219T mutations, and the heterozygous p.Q167fsX186 frameshift allele was the only mutation detected in the affected individual from an additional pedigree. For the remaining family no mutations were detected. The patient homozygous for the p.A102V mutation had glucosuria of 65.6 g/1.73 m2/24 h, evidence of renal sodium wasting, mild volume depletion, and raised basal plasma renin and serum aldosterone levels. Our findings confirm previous observations that in FRG, transmitted as a codominant trait with incomplete penetrance, most mutations are private. In the only patient with massive glucosuria in our cohort there was evidence evocative of renin–angiotensin aldosterone system activation by extracellular volume depletion induced by natriuresis. Definite proof of renin–angiotensin aldosterone system activation in FGR should rely on evaluation of additional patients with massive glucosuria.

glucosuria, renal, SLC5A2, SGLT2, mutation 

Tissue Doppler imaging in the evaluation of left ventricular function in young adults with autosomal dominant polycystic kidney disease

Almeida EA, Oliveira EI, Lopes JA, Almeida AG, Prata MM.

Serviço de Nefrologia e Transplantação Renal, Hospital de Santa Maria, Lisboa, Portugal.

Am J Kidney Dis. 2006 Apr;47(4):587-92.

BACKGROUND: Hypertension and increased left ventricular mass index (LVMI) have been reported in patients with early stages of autosomal dominant polycystic kidney disease (ADPKD). Whether these abnormalities are associated with diastolic dysfunction in this stage remains to be established. The aim of the study is to evaluate diastolic function in young normotensive patients with ADPKD by using tissue Doppler imaging (TDI), the most sensitive method available to date.

METHODS: Thirty-two young clinically normotensive patients aged 21 to 30 years were compared with 23 controls with similar ages. Ambulatory blood pressure measurement (ABPM) was performed to confirm normal blood pressure. Subsequently, patients and controls underwent echocardiography using transmitral Doppler and TDI.
RESULTS: LVMI was greater in patients with ADPKD than controls (89.3 +/- 17.7 versus 77.6 +/- 15.9 g/m2; P < 0.02). No significant differences were found in transmitral Doppler and TDI results. When ABPMs were taken into account, 11 patients had mild hypertension and showed increased LVMI and decreased early diastolic peak velocity (E wave: 67.0 +/- 12.0 cm/s in hypertensive patients with ADPKD versus 81.4 +/- 3.3 cm/s in normotensive patients with ADPKD versus 79.3 +/- 2.9 cm/s in controls; P < 0.04) and decreased TDI peak early diastolic annular velocity (11.6 +/- 2.8 cm/s in hypertensive patients with ADPKD versus 13.2 +/- 1.6 cm/s in normotensive patients with ADPKD versus 13.4 +/- 1.6 in controls; P < 0.05).

CONCLUSION: Diastolic dysfunction is not a prominent sign in young normotensive patients with ADPKD.

PMID: 16564936 [PubMed - indexed for MEDLINE]

Renal diseases: a 27-year renal biopsy study

Carvalho E, do Sameiro Faria M, Nunes JP, Sampaio S, Valbuena C.

Department of Nephrology, Hospital Sao Joao, Faculty of Medicine, University of Porto, Portugal.

J Nephrol. 2006; 19(4): 500-7

BACKGROUND: Data from registries of renal biopsy (RB), currently an important source for diagnosing renal disease, are available for a number of countries, but different patterns seem to exist in different countries. METHODS: We reviewed the records of all patients who underwent an RB at our institution over a 27-year period (January 1, 1977, to December 31, 2003), in northern Portugal, a European region with a predominantly Caucasian population. We aimed at identifying patterns of glomerular disease frequency, as well as the corresponding changes over time. The patients were grouped for analysis in 9-year intervals: period A (1977 through 1985), period B (1986 through 1994) and period C (1995 through 2003). RESULTS: Nephrotic syndrome was the most common clinical presentation for RB (42.0%), followed by urinary abnormalities (28.5%), acute renal failure (9.7%), chronic renal failure (9.3%) and nephritic syndrome (9.3%). Primary glomerulonephritis (GN) was the most common type of kidney disease in the present study, representing 50.4% of all renal pathology, followed by secondary GN (29.4%) and vascular and tubulointerstitial diseases (14.0%). The relative frequency of secondary GN and vascular and tubulointerstitial diseases increased significantly over time, and so did IgA nephropathy, the most common type of primary glomerular disease in the present study (31.2%). Focal and segmental glomerulosclerosis represented 6.9% of primary glomerular disease, and its frequency did not increase in the time period under study. Regarding secondary glomerular diseases, apparent changes were noted in the incidence of a number of diseases, including vasculitis, thin glomerular basement membrane disease and Henoch-Schonlein pur-pura. A somewhat similar situation was noted with vascular and tubulointerstitial diseases. CONCLUSIONS: We conclude that, as occurs in other European and Asiatic populations, and unlike the findings in the American continent, IgA nephropathy is the most frequent glomerular disease in our population.

PMID: 17048208 [PubMed - in process]

Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol

Neves PL, Trivino J, Casaubon F, Santos V, Mendes P, Romao P, Bexiga I, Bernardo I.

Fresenius Medical Care, Algarve (Faro, Portimao and Tavira), Portugal.

Int Urol Nephrol. 2006; 38(1) :175-7

In patients on chronic hemodialysis (CHD), hyperparathyroidism (HPTH) is associated with anemia and resistance to erythropoietin (EPO). In the last few years, calcitriol intravenously (IV) has been used with success in the treatment of the HPTH, secondary to chronic renal failure. However, the effects of calcitriol on the hematological parameters of these patients have never been well evaluated. This study included 11 elderly CHD patients (f = 6, m = 5; mean age = 73.6 years, mean time on CHD = 42.8 months) with HPTH under EPO therapy (IV). They were treated for 12 months with calcitriol IV (mean dose = 2.33 mcg/pt/week). Patients with iron deficiency anemia (ferritin < 200 ng/ml) were excluded. The patients were compared before and after 12 months of calcitriol treatment, with respect to several laboratory parameters and with respect to EPO dose. A paired t-test was used. After treatment, we found a decrease of PTH (634 vs. 418 pg/ml, P = 0.029); the serum calcium increased (8.8 vs. 9.9 mg/dl, P = 0.002); no differences were noted in the plasma levels of alkaline phosphatase, phosphorous, BUN, creatinine, Na and K. Mean levels of Hb (10.2 vs. 11.4 g/dl, P = 0.004) and the Hct (30 vs. 34.3, P = 0.004) increased after 12 months of calcitriol; the levels of serum iron (70 vs. 78 microg/dl, P = ns) and ferritin (531 vs. 785 ng/ml, P = ns) and the EPO dose (105 vs. 100 U/kg/week, P = ns) were similar before and after treatment. Our data show that the treatment of HPTH in CHD elderly patients with calcitriol can increase Hb level without increasing EPO dose.

PMID: 16502078 [PubMed - indexed for MEDLINE]

Effectiveness of weekly darbepoetin alfa in the treatment of anaemia of HIV-infected haemodialysis patients

Lucas C, Carrera F, Jorge C, Boquinhas H, Pais MJ.

Department of Nephrology, Hospital de Santa Cruz, Carnaxide and Dialysis Unit, Eurodial, Leiria, Portugal.

Nephrol Dial Transplant 2006; 21: 3202-3206

BACKGROUND: Anaemia is aggravated by the coexistence of chronic kidney disease (CKD) in patients infected with human immunodeficiency virus (HIV). Darbepoetin alfa effectively alleviates CKD-associated anaemia with less frequent dosing than recombinant human erythropoietin (EPO). The current study aimed to determine the efficacy, safety and cost-effectiveness of darbepoetin alfa compared with erythropoietin alfa (EPO-alfa) for treatment of anaemia in HIV-infected subjects receiving haemodialysis. METHODS: An open label, single arm, prospective study of 12 haemodialysis subjects with HIV infection was conducted for a duration of 6 months after switching from intravenous (i.v.) EPO-alfa two/three times weekly to i.v. darbepoetin alfa once weekly. The primary end point was the proportion of patients maintaining haemoglobin (Hb) levels >/=11 g/dl while a weekly dose of darbepoetin alfa was a secondary end point.

RESULTS: Darbepoetin alfa, as effectively as EPO-alfa maintained the proportion of the subjects having Hb levels >/=11 g/dl at an average weekly dose of 40.60 microg compared with an equivalent dose of 51.84 microg for EPO-alfa. Antiretroviral therapy and HIV infection stage remained the same for each specific patient throughout the study period, including the last 6 months of EPO-alfa therapy. No difference in the incidence of adverse effects was observed after switching from EPO-alfa to darbepoietin alfa.

CONCLUSIONS: Lower doses of darbepoetin alfa at extended dosing interval is as safe and effective as EPO-alfa for treating anaemia, suggesting that darbepoetin alfa is a more cost-effective therapeutic alternative to EPO-alfa in the management of anaemia associated with HIV infection in subjects receiving haemodialysis.

PMID: 16891651 [PubMed - as supplied by publisher]

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The efficacy of intravenous darbepoetin alfa administered once every 2 weeks in chronic kidney disease patients on haemodialysis

Carrera F, Oliveira L, Maia P, Mendes T, Ferreira C.

Dialysis Unit, Eurodial, Leiria, Portugal.

Nephrol Dial Transplant 2006; 21: 2846–2850

BACKGROUND: It is becoming increasingly more common to administer intravenous (i.v.) darbepoetin alfa to haemodialysis (HD) patients at less frequent dosing intervals in routine clinical practice. This study investigated extending the dosing interval for i.v. darbepoetin alfa treatment from once a week (QW) to once every 2 weeks (Q2W) at the same dose in order to maintain target haemoglobin (Hb) concentrations (11-13 g/dl). METHODS: Stable HD patients in routine clinical practice receiving i.v. darbepoetin alfa QW for a period of 6 months (n = 105) (treatment period 1) were switched to i.v. Q2W darbepoetin alfa for a further 6 months (treatment period 2) (n = 90). The dose of i.v. darbepoetin alfa was titrated to maintain Hb concentrations between 11 and 13 g/dl throughout the full 12-month study period.

RESULTS: The mean change in Hb for treatment period 2 was 0.04 +/- 1.1 g/dl (+/-SD), which was not clinically relevant (11.7 +/- 0.8 g/dl vs 11.7 +/- 1.0 g/dl; P = 0.8). The mean weekly doses of darbepoetin alfa were similar throughout the treatment periods (34.0 +/- 17.1 microg/week vs 32.1 +/- 17.3 microg/week; P = 0.3, respectively for QW and Q2W dosing). Intravenous darbepoetin alfa was well tolerated.

CONCLUSIONS: The treatment of renal anaemia in HD patients with i.v. Q2W darbepoetin alfa effectively and safely maintains Hb concentrations at a less frequent dosing regimen than observed with QW administration. Dose requirements for i.v. darbepoetin alfa administered QW or Q2W were not different. The results of this study demonstrate that i.v. darbepoetin alfa administered Q2W is an effective regimen for HD patients requiring anaemia treatment in routine clinical practice.

PMID: 16891642 [PubMed - as supplied by publisher]

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Tailored Anaemia Management in Patients with Chronic Kidney Disease

Fernando Carrera

Senior Consultant Nephrologist, Eurodial, Dialysis Unit, Leiria

European Renal & Genito-Urinary Disease 2006

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An assessment of the RIFLE criteria for acute renal failure following myeloablative autologous and allogeneic haematopoietic cell transplantation

Lopes JA, Jorge S, Silva S, de Almeida E, Abreu F, Martins C, do Carmo JA, Lacerda JF, Prata MM.

Bone Marrow Transplant. 2006 Sep;38(5):395.

PMID: 16915229 [PubMed - indexed for MEDLINE]

Acute renal failure following myeloablative autologous and allogeneic hematopoietic cell transplantation

Lopes JA, Jorge S, Silva S, de Almeida E, Abreu F, Martins C, do Carmo JA, Lacerda JF, Prata MM.

Bone Marrow Transplant. 2006 Nov;38(10):707. Epub 2006 Oct 2.

PMID: 17013425 [PubMed - indexed for MEDLINE]

Blunted renal dopaminergic system activity in HgCl(2)-induced membranous nephropathy

Sampaio-Maia B, Moreira-Rodrigues M, Serrao P, Pestana M.

Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Alameda Prof. Hernani Monteiro, 4200-319, Porto, Portugal.

Life Sci. 2006; 78(11): 1246-55

The present study evaluated the possible role of the renal dopaminergic system in the sodium retention of HgCl(2)-induced nephrotic syndrome. The time courses of urinary excretion of sodium, protein, dopamine and the precursor l-3,4-dihydroxyphenylalanine (l-Dopa) were evaluated in HgCl(2)-treated and control rats up to day 21. The renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine, was evaluated during negligible proteinuria accompanied with enhanced sodium retention (day 7), increased proteinuria accompanied with greatest sodium retention (day 14) as well as during increased proteinuria accompanied with negative sodium balance (day 21). Also, the influence of volume expansion (VE, 5% bw) and the effects of the D(1)-like agonist fenoldopam (10 mug kg bw(-1) min(-1)) on natriuresis and on proximal tubular Na(+),K(+)-ATPase activity were examined on day 14. The daily urinary dopamine output and urinary dopamine/l-Dopa ratios were reduced in HgCl(2)-treated rats from day 2 and beyond. This was accompanied by a marked decrease in renal AADC throughout the study. During VE, the fenoldopam-induced inhibition of proximal tubular Na(+),K(+)-ATPase activity was similar between HgCl(2)-treated and control rats. However, the urinary sodium excretion during fenoldopam infusion was markedly increased by 60% to 120% in control rats but was not altered in HgCl(2)-treated rats. It is concluded that HgCl(2) nephrosis is associated with a blunted renal dopaminergic system activity. However, the lack of renal dopamine in HgCl(2) nephrosis does not appear to be related with the overall renal sodium retention in a state of proteinuria.

PMID: 16182313 [PubMed - as supplied by publisher]

Medullar expression of type-A natriuretic peptide receptor in an animal model of hypertension induced by renal mass ablation

Araujo CS, Albuquerque RR Jr, Rodrigues MM, Maia BS, Moreira AF, Pestana M.

Unidade de Investigacao e Desenvolvimento de Nefrologia, Faculdade de Medicina, Porto, Portugal.

Rev Port Cardiol. 2006; 25(4): 419-27

INTRODUCTION: The biological activity of the natriuretic peptide (NP) system is dependent on the balance between NP tissue levels and the local expression of their receptors. In the kidney, the natriuretic peptide receptor type A (NPR-A) is the principal receptor mediating NP activity and is mainly expressed in the renal medulla. An increase in circulating NP levels is well documented in chronic renal failure (CRF); however, the renal expression of NPR-A has not been evaluated in this condition.

METHODS: Wistar-Han rats were submitted to right nephrectomy plus ablation of both poles of the left kidney (3/4nx; n=27) or were sham operated (Sham; n=22) and followed for up to 26 weeks post surgery. Blood pressure measurements were performed weekly. Two, 10 and 26 weeks after surgery, renal sodium and creatinine excretion were evaluated and the kidneys removed for NPR-A mRNA quantification by real-time PCR. The results of mRNA quantification are expressed in arbitrary units (AU) set as the mean value of the Sham group (Sham=1 AU), after normalization for GAPDH (p<0.05). weeks after surgery) and in elevated fractional sodium excretion (+270%, 26 weeks after surgery). Although sodium intake was similar in 3/4nx and Sham rats, blood pressure was higher in 3/4nx rats and increased progressively throughout the study. This was accompanied by a marked decrease in NPR-A mRNA levels in the renal medulla from 3/4nx animals at 2, 10 and 26 weeks post surgery.

Conclusion: In 3/4nx rats, the expression of NPR-A in the renal medulla of the remnant kidney is markedly reduced from 2 weeks up to 26 weeks post surgery. It is suggested that this may contribute to the progressive increase in blood pressure, as well as to the renal fibrosis observed in 3/4nx rats.

PMID: 16869207 [PubMed - indexed for MEDLINE]

Renal transplantation in patients over 60 years of age: a single-center experience

Pedroso S, Martins L, Fonseca I, Dias L, Henriques AC, Sarmento AM, Cabrita A.

Nephrology and Transplant Departments, Hospital Geral de Santo Antonio, Largo Professor Abel Salazar, 4050-011 Porto, Portugal.

Transplant Proc. 2006 Jul-Aug;38(6):1885-9.

The prevalence of end-stage renal disease (ESRD) increases with advancing age. In most countries renal transplant recipients are getting older, too. Transplantation must be considered for ESRD patients older than 60 years; however, there are few data regarding outcomes in this population. We retrospectively reviewed the clinical course of recipients aged > or =60 years (n = 43) who underwent primary or repeated grafts from August 1988 to December 2004. We then compared recipient and donor characteristics as well as graft and patient survivals with recipients aged 18 to 59 years (n = 1058) who were transplanted during the same time. Donor age tended to be higher among the oldest recipient group (P < .001). Mean follow-up was significantly shorter in the group aged > or =60 years (P < .001), as our institution only recently has frequently accepted patients > or =60 years. Older recipients showed more frequent delayed graft function (P = .007), longer initial hospitalization (P = .005), and a significantly lower incidence of posttransplant acute rejection episodes (P = .015). Patient (P = .057), graft (P = .407), and death-censored graft (P = .649) survivals were not different between the two groups. Seven recipients aged > or =60 years died; the main cause of which was cardiovascular in origin. The loss of organs (n = 11) in the older patients was mainly due to death with a functioning kidney (54.5%). Our results confirm that renal transplant must be considered in selected patients older than 60 years as patient and graft survivals are similar to those of younger patients.

PMID: 16908313 [PubMed - indexed for MEDLINE]

Impact of hepatitis C virus on renal transplantation: association with poor survival

Pedroso S, Martins L, Fonseca I, Dias L, Henriques AC, Sarmento AM, Cabrita A.

Nephrology and Transplant Departments, Hospital Geral de Santo Antonio, Largo Professor Abel Salazar, 4050-011 Porto, Portugal.

Transplant Proc. 2006 Jul-Aug;38(6):1890-4

Data concerning the effect of hepatitis C virus (HCV) infection on the long-term outcome of patient and allograft survival are conflicting. We performed a retrospective study including all renal transplant recipients who underwent the procedure at our center between July 1983 and December 2004. We compared HCV-positive (n = 155) versus HCV-negative (n = 1044) recipients for the prevalence of anti-HCV, patient/donor characteristics, and graft/patient survival. The prevalence of HCV-positive patients was 12%. The anti-HCV positive recipients displayed a longer time on dialysis (P < .001), more blood transfusions prior to transplant (P < .001), and a higher number of previous transplants (P < .001). There were no differences in the incidence of acute rejection between the two groups. Patient (P = .006) and graft survival (P = .012) were significantly lower in the HCV-positive than the HCV-negative group. Graft survival censored for patient death with a functioning kidney did not differ significantly between HCV-positive and HCV-negative recipients (P = .083). Death from infectious causes was significantly higher among the HCV-positive group (P = .014). We concluded that HCV infection had a significant detrimental impact on patient and renal allograft prognosis. Death from infectious causes was significantly more frequent among HCV-positive than the non-HCV population.

PMID: 16908314 [PubMed - indexed for MEDLINE]

Simultaneous pancreas-kidney transplantation: five-year results from a single center

Martins L, Pedroso S, Henriques AC, Dias L, Sarmento AM, Seca R, Oliveira F, Dores J, Lhamas A, Coelho T, Ribeiro A, Esteves S, Pereira R, Almeida R, Amil M, Cabrita A, Teixeira M.

Nephrology Department, Hospital Santo Antonio, Largo Professor Abel Salazar, 4050-011 Porto, Portugal.

Transplant Proc. 2006 Jul-Aug;38(6):1929-32.

We report the 5-year results of our simultaneous pancreas-kidney transplantation (SPKT) program, started on May 2, 2000. Forty-two SPKT were performed on 42 type I diabetic patients with chronic renal failure. The procedure was performed with enteric diversion and vascular anastomosis to the iliac vessels. Immunosuppressive protocol included antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The 24 women and 18 men had a mean age of 33.5 +/- 6.3 years and mean 22.8 +/- 14.2 years time of diabetes evolution. Forty patients had been on dialysis for 34.3 +/- 24.1 months, and two were preemptive transplantations. Acute rejection episodes were treated in eight patients (19.1%): in three cases they affected both organs; in two only the kidney was affected; and the other three were pancreas graft rejections. The incidence of postoperative complications requiring re-operation was 42.9%, mostly pancreas graft related. Two patients died, one due to cardiovascular disease; the other was transplant related. Three kidney grafts were lost, and the causes were immunologic, thrombosis, and patient death. Pancreas graft loss occurred in seven patients: thrombosis (n = 3); infection (n = 3); immunologic (n = 1). The patients with surviving grafts were doing well, with normal kidney and pancreas function: serum creatinine = 0.89 +/- 0.15 mg/dL; fasting blood glucose = 79 +/- 16 mg/dL; HbA1c = 4.7 +/- 1.1%. The 1-year patient, kidney, and pancreas survival rates were 97.3%, 94.6%, and 83.8% and 5-year values, 91.7%, 89.2%, and 78.7%, respectively. In conclusion, these results are similar to the most recent UNOS/IPTR reports, leading us to consider our experience with SPKT very positive.

PMID: 16908326 [PubMed - indexed for MEDLINE]

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