Publicações - 2004

Renal Dopamine and Salt Sensitivity of Blood Pressure in IgA Nephropathy

Pestana M, Santos J, Santos A, Coroas A, Correia F, Serrao P, Valbuena C, Soares-Da-Silva P.

Department of Nephrology, Faculty of Medicine, Porto, Portugal.

Kidney Blood Press Res. 2004; 27(2): 78-87en Nutr. 2004; 14(3): 157-63

BACKGROUND: Patients with chronic glomerulonephritis exhibit salt-sensitive (SS) hypertension. In the early stage, however, the exact characteristics are still unclear. A decrease in renal dopamine production under basal conditions or after a sodium load has been reported in a subset of patients with SS primary hypertension. AIMS: The present study examined 17 untreated IgA-N patients with near-normal renal function, to determine whether salt sensitivity appears before hypertension and whether this sensitivity is related to renal dopamine production. METHODS: Daily urinary excretion of dopamine, the amine precursor - L-DOPA, and metabolites was monitored in conditions of basal sodium ingestion, followed by three consecutive 5-day periods of 100, 20 and 350 mmol/day sodium intake. The sodium sensitivity index (SSI) was evaluated in each patient. In addition, the patients were considered SS when showing an increase >/=5 mm Hg in 24-hour mean BP when they changed from a 20- to a 350-mmol/day sodium diet. RESULTS: Urinary dopamine output was lower in SS than in salt-resistant patients throughout the study (p < 0.001). This was accompanied by lower creatinine clearance values and higher urinary protein excretion in SS IgA-N patients. A strong negative relationship was observed in these 17 IgA-N patients between the SSI and the daily urinary excretion of dopamine in conditions of both 20 mmol/day sodium intake (r(2) = 0.592; p = 0.0003) and 350 mmol/day sodium diet (r(2) = 0.352; p = 0.01). However, urinary dopamine output varied appropriately throughout the study in SS patients, in agreement with changes in sodium intake. CONCLUSION: We conclude that in IgA-N patients, a rightward shift in the 'pressure natriuresis' can appear before hypertension and is related with a reduced renal production of dopamine. It is suggested that decreased renal dopamine synthesis in SS IgA-N patients results from acquired tubulointerstitial injury. In contrast to what has been found in SS primary hypertension, renal dopamine may behave appropriately in SS IgA-N patients, as a compensatory hormone.

Copyright 2004 S. Karger AG, Basel

The effect of dietary sodium restriction on neurohumoral activity and renal dopaminergic response in patients with heart failure

Alvelos M, Ferreira A, Bettencourt P, Serrao P, Pestana M, Cerqueira-Gomes M, Soares-Da-Silva P.

Unit of Cardiovascular Research and Development, Piso 9, Porto, Portugal. malvelos@netcabo.pt

Eur J Heart Fail. 2004; 6(5): 593-9

BACKGROUND: This work evaluates the effect of a low-sodium diet on clinical and neurohumoral parameters and on renal dopaminergic system activity in heart failure (HF) patients.

METHODS: We included 24 patients with mild-to-moderate stable HF with left ventricle ejection fraction <40%. Twelve patients were studied before and after a 15-day low-sodium diet; 12 maintained their usual diet. Serum sodium and creatinine, plasma l-DOPA, dopamine, its metabolites, BNP and aldosterone, and 24-h urinary sodium, creatinine, l-DOPA, dopamine and metabolites were measured.

RESULTS: The two groups were matched respecting to demographic and clinical parameters. Low-sodium diet caused significant reductions in weight, 24-h urinary volume and sodium and sodium fractional excretion. Renal delivery of l-DOPA and urinary excretion of l-DOPA significantly decreased while dopamine and metabolites were not affected. Urinary dopamine/l-DOPA and urinary dopamine/renal delivery of l-DOPA ratios increased, plasma l-DOPA decreased and plasma dopamine increased. Plasma aldosterone slightly rose, BNP decreased and noradrenaline and adrenaline increased. NYHA functional class was not affected by sodium restriction. Controls showed no differences.

CONCLUSIONS: These results suggest that sodium restriction leads to activation of antinatriuretic antidiuretic systems in HF patients. However, renal ability to synthesize dopamine is increased in this condition, probably as a counter-regulatory mechanism.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15302007 [PubMed - indexed for MEDLINE]

Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6: relationship with peritoneal transport

Rodrigues A, Martins M, Santos MJ, Fonseca I, Oliveira JC, Cabrita A, Melo e Castro J, Krediet RT.

Nephrology Department, Hospital Geral de Santo Antonio, Porto, Portugal. ar.cbs@mail.telepac.pt

Adv Perit Dial. 2004; 20: 8-12

Peritoneal hyperpermeability has been associated with increased levels of
effluent vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6).
Mesothelial cells can produce various vasoactive substances besides VEGF. A large mesothelial mass may possibly lead to high dialysate VEGF concentrations and may partly explain some cases of peritoneal hyperpermeability during a patient's early months on peritoneal dialysis (PD). Early peritoneal fast transport may therefore not necessarily be associated with systemic inflammation. To investigate the relationship of effluent markers and peritoneal transport, we measured the appearance rates of cancer antigen 125 (CA125), VEGF, and IL-6 in 4-hour effluents from 69 peritoneal equilibration tests (PETs) using 3.86% glucose solution. At the same time, we measured serum VEGF and IL-6. Our analyses included an early group (EG), whose members had been on PD for 4.6 +/- 3.3 months, and a later group (LG), whose members had been on PD for 30 +/- 17 months. In EG, dialysate-to-plasma creatinine at 4 hours (D/P(Cr240)) correlated significantly with effluent CA125/min (r = 0.51, p = 0.006) and VEGF/min (r = 0.57, p = 0.001), but not with serum VEGF or IL-6. The values of CA125/min and VEGF/min also correlated (r = 0.40, p = 0.034). Fast transporters in EG had higher effluent CA125 (p = 0.057) and VEGF (p = 0.0001), but not serum or effluent IL-6. In LG, D/P(Cr240) again correlated significantly with dialysate VEGF (r = 0.51, p = 0.009), but not with CA125. Fast transporters in LG tended to have higher levels of serum and effluent IL-6 and effluent VEGF. We conclude that fast solute transport rates at the beginning of PD are associated with signs of a large mesothelial cell mass and not consistently associated with higher systemic IL-6. The VEGF produced by mesothelial cells can mediate early peritoneal hyperpermeability in some populations. Later, mesothelial mass is lost and is no longer related to increased intraperitoneal VEGF or IL-6.


PMID: 15384786 [PubMed - in process]

Novel compound heterozygous mutations in SLC5A2 are responsible for autosomal recessive renal glucosuria

Calado J, Soto K, Clemente C, Correia P, Rueff J.

Department of Genetics, Faculty of Medical Sciences, New University of Lisbon, Rua da Junqueira 96, 1349-008 Lisbon, Portugal. jcalado.gene@fcm.unl.pt

Hum Genet. 2004; 114(3): 314-6

Familial renal glucosuria is an inherited renal tubular disorder. A homozygous nonsense mutation in the SLC5A2 gene, encoding the sodium/glucose co-transporter SGLT2, has recently been identified in an affected child of consanguineous parents. We now report novel compound heterozygous mutations in the son of non-consanguineous parents. One allele has a p.Q167fsX186 mutation, which is expected to produce a truncated protein, and the other a p.N654S mutation involving a highly conserved residue. These findings confirm that mutations in the SLC5A2 gene are responsible for recessive renal glucosuria.

End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors

Lobato L, Beirao I, Silva M, Fonseca I, Queiros J, Rocha G, Sarmento AM, Sousa A, Sequeiros J.

Department of Nephrology, Hospital Geral de Santo Antonio, UnIGENe, Institute for Molecular and Cell Biology, Centro de Estudos de Paramiloidose, Porto, Portugal. llobato@netcabo.pt

Amyloid. 2004; 11(1): 27-37

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years. Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.

PMID: 15185496 [PubMed - in process]

Kidney and anemia in familial amyloidosis type I

Beirao I, Lobato L, Costa PM, Fonseca I, Mendes P, Silva M, Bravo F, Cabrita A, Porto G.

Department of Nephrology, Santo Antonio General Hospital, Porto, Portugal. bbeirao@iol.pt

Kidney Int. 2004; 66(5): 2004-9

BACKGROUND: Familial amyloid polyneuropathy (FAP) type I is caused by a mutated transthyretin (TTR V30M) and characterized by a sensorimotor and autonomic neuropathy. Renal, cardiac, and ocular abnormalities can also occur. Anemia has been described in previous reports, but its prevalence in Portuguese FAP patients is not precisely known. The aim of this study was to estimate the prevalence of anemia in FAP type I Portuguese patients and to evaluate the contribution of erythropoietin (Epo) to its genesis. METHODS: A retrospective cross-sectional study was undertaken to determinate the prevalence and characteristics of anemia in 165 FAP patients. For comparison analysis, 3 control groups were also evaluated, 1 group of 46 apparently healthy subjects, 1 group of 17 asymptomatic carriers of FAP-trait, and a group of 14 non-FAP patients with chronic renal insufficiency. Serum Epo levels were analyzed in all groups. RESULTS: Anemia was present in 24.8% of symptomatic FAP patients. Iron stores, B12 vitamin, and serum folate levels were normal. FAP patients presented significantly lower serum Epo levels than healthy controls (P= 0.003). Epo levels were found lower than expected for the degree of anemia and in 17.5% were undetectable. Low Epo values were observed independently of the presence of renal failure or anemia, and sometimes preceded clinical disease. CONCLUSION: Anemia in FAP type I is a common manifestation. The results clearly suggest a defective endogenous Epo production in the genesis of the anemia.

PMID: 15496172 [PubMed - in process]

Enzyme replacement therapy administered during hemodialysis in patients with Fabry disease

Kosch M, Koch HG, Oliveira JP, Soares C, Bianco F, Breuning F, Rasmussen AK, Schaefer RM.

Department of Internal Medicine D, University of Munster, Munster, Germany. koschm@uni-muenster.de

Kidney Int. 2004; 66(3): 1279-82

BACKGROUND: Enzyme replacement treatment with recombinant human alpha-galactosidase A (r-halphaGalA) is now available for patients with Fabry disease, many of whom are on maintenance hemodialysis. Because r-halphaGalA must be infused over several hours, administering the enzyme during dialysis would save a day of treatment for patients receiving both therapies. However, these procedures have never been combined due to concerns about possible loss of enzyme in the dialysate. METHODS: Ten Fabry patients received r-halphaGalA (1 mg/kg body weight continuously infused over 4 hours) during dialysis and separately in the interval between dialysis treatments. Plasma activity of r-halphaGalA was measured at baseline and then every hour for both procedures. In two patients, a third r-halphaGalA infusion during dialysis with a high-flux membrane was followed. RESULTS: The rise in plasma concentrations of r-halphaGalA during infusion and the steady-state levels reached were comparable for enzyme administrations with or without dialysis. The trend for the somewhat higher activities during hemodialysis was explained by volume contraction due to ultrafiltration. With the use of a high-flux dialyzer, the plasma r-halphaGalA activities were identical to those that were observed during low-flux dialysis. CONCLUSIONS: Administration of r-halphaGalA during hemodialysis is not associated with a reduced activity of r-halphaGalA therapy in patients with Fabry disease. Replacement therapy with r-halphaGalA may therefore be performed during hemodialysis without apparent loss of enzyme into the dialysate.

Publication Types:
Clinical Trial

PMID: 15327428 [PubMed - indexed for MEDLINE]

A simple vascular calcification score predicts cardiovascular risk in haemodialysis patients

Adragao T, Pires A, Lucas C, Birne R, Magalhaes L, Goncalves M, Negrao AP.

Nefroclinica-Estoril, Rua Vale de S Rita, 19, 2765-293 Esteril, Portugal.

Nephrol Dial Transplant. 2004; 19(6): 1480-8

BACKGROUND: Cardiovascular morbidity and mortality are highly prevalent in haemodialysis (HD) patients and have been recently associated with vascular calcifications. The objective of our study was to assess the value of a simple vascular calcification score for the prediction of cardiovascular death, cardiovascular hospitalizations and fatal and non-fatal cardiovascular events in HD patients, and to correlate this score with cardiovascular disease and with other known predictors of vascular disease. METHODS: In this observational, prospective study 123 chronic HD patients (75 males and 48 females; 20% diabetic) were included, who were on low-flux HD treatment for 46.6+/-52 months (mean+/-SD). We set up a simple vascular calcification score based on plain radiographic films of pelvis and hands. Brachial pulse pressure and mean arterial pressure (MAP) were measured and cardiovascular events and hospitalization episodes were assessed.

RESULTS: During an observational period of 37 months there were 17 cardiovascular deaths; 28 patients needed cardiovascular hospitalizations and 32 patients suffered fatal and non-fatal cardiovascular events. Coronary artery disease was diagnosed in 43 patients (35%), peripheral arterial disease in 33 patients (26.8%), cerebrovascular disease in 16 patients (13%) and vascular disease (coronary artery disease or peripheral arterial disease or cerebral vascular disease) in 61 patients (49.6%). By binary logistic regression, diabetes (P = 0.01), male sex (P<0.001), age (P = 0.02), HD duration (P = 0.02) and MAP (P = 0.03) were independently associated with a vascular score >/=3. This score >/=3 was independently associated with coronary artery disease (P = 0.008), peripheral arterial disease (P<0.001) and vascular disease (P = 0.001). Patients with a vascular calcification score >/=3 had a 3.9-fold higher risk of cardiovascular mortality (P = 0.03), a 2.8-fold higher risk of cardiovascular hospitalizations (P = 0.02) and a 2.3-fold higher risk of fatal or non-fatal cardiovascular events (P = 0.04). CONCLUSIONS: The present vascular calcification scoring represents a simple tool for the assessment of cardiovascular risk related with vascular calcifications in chronic HD patients.

End-stage renal disease and dialysis in hereditary amyloidosis TTR V30M: presentation, survival and prognostic factors

 Lobato L, Beirao I, Silva M, Fonseca I, Queiros J, Rocha G, Sarmento AM, Sousa A, Sequeiros J.

Department of Nephrology, Hospital Geral de Santo Antonio, UnIGENe, Institute for Molecular and Cell Biology, Centro de Estudos de Paramiloidose, Porto, Portugal. llobato@nctcabo.pt

Amyloid. 2004; 11(1): 27-37

Classical familial amyloid polyneuropathy may have a course with progressive renal impairment. We studied 62 patients (24 males, 38 females) with FAP, transthyretin variant V30M, and end-stage renal disease (ESRD) treated with hemodialysis, all referred to a single center over a period of 11 years.
Clinical course, morbidity and survival after dialysis were analyzed. Patient's mean age at first dialysis was 51.5 +/- 10.7 years, and mean duration of neuropathy was 10.2 +/- 3.8 years. The most frequent form of presentation of FAP nephropathy was nephrotic proteinuria with renal dysfunction. In the year prior to dialysis, renal function declined rapidly, and fluid overload was the main indication to initiate treatment. The presence of decubitus ulcers, significant disability, venous catheter for definitive vascular access for long-term treatment, and permanent bladder catheter, were related to death during the first year of dialysis. The mean duration of renal replacement therapy was 21 months, with a 54.5% one year, and 38.4% two year treatment survival. However, when the duration of neurological symptoms at first dialysis exceeded 10 years, survival was significantly lower. Infections, (41% were decubitus ulcers with sepsis) were the cause of early, as well as late mortality. Early creation of vascular access for hemodialysis, surveillance of skin wounds, and intervention on neurogenic bladder are essential to improve the prognosis of ESRD in FAP.

PMID: 15185496 [PubMed - in process]

Cyclosporine enhances salt sensitivity of body water composition as assessed by impedance among psoriatic patients with normal renal function

Coroas AS, de Oliveira JG, Magina S, Santos J, Pestana M, de Almeida MD.

Nephrology Department, S Joao Hospital, Porto, Portugal. jcasimiro@mail.telepac.pt

J Ren Nutr. 2004; 14(4): 226-32

OBJECTIVE: Cyclosporine (CsA) therapy may be accompanied by a significant increase in blood pressure, either sodium (Na+) independent or Na+ dependent. The relationship between Na+ intake and body water distribution among patients treated with CsA has not been evaluated. We report the study, by bioelectrical impedance analysis (BIA), of water composition changes after dietary salt manipulations both before and during CsA treatment of psoriatic patients. METHODS: Ten normotensive psoriatic patients, ages 37 +/- 12 years 19 to 54), with normal renal function were included. Each patient was assessed by BIA in 2 phases, before (phase 1) and during (phase 2) CsA therapy (3 mg/kg/day). In both phases, each patient was assessed in basal conditions (basal1 and basal2), on day 7 of a low-sodium diet (LS1 and LS2; 20 mEq/day) and on day 7 of a high-sodium diet (HS1 and HS2; 350 mEq/day). Plasma creatinine (Pcr), urinary volume excretion (Uv), urinary sodium (UNa+), urinary potassium (UK+), urinary osmolality (UOsmo), weight (Wt), resistance (R), reactance (Xc), total body water (TBW), extracellular water (ECW), intracellular water (ICW), Na:K exchangeable (Nae:Ke), phase angle (PA), and body cell mass (BCM) were evaluated. Blood pressure was monitored during 24 hours on the last day of each diet. Paired Student's t-test was used to analyze the different phases.

RESULTS: Before CsA treatment, Wt, TBW and Nae:Ke were lower during LS1 than during basal1, whereas TBW was higher during HS1 than during LS1. During CsA, Wt, TBW, ECW, and Nae:Ke were lower during LS2 than during basal2, whereas ICW and PA were higher during LS2 than during basal2. HS2 showed higher TBW, ECW, and Nae:Ke and lower ICW, PA, and BCM than during LS2. Systolic blood pressure was higher during HS2 than during LS2 or HS1. In addition, diastolic blood pressure was higher during HS2 than during HS1. CONCLUSION: Body hydration status was more sensitive to dietary salt fluctuations during CsA treatment than without CsA, and a high-sodium diet seemed to enhance the CsA-induced hypertension side effect. Moreover, patients on low sodium intake under CsA treatment displayed neither any disturbance of body water composition nor any blood pressure change. Our data suggest that a low sodium intake might be very useful in preventing undesirable pressure and volume changes brought about by CsA treatment.

PMID: 15483783 [PubMed - in process]

Sequential body composition analysis by impedance early post-kidney transplantation.

Coroas A, Oliveira JG, Sampaio S, Borges C, Tavares I, Pestana M, De Almeida MD.

Faculty of Food and Nutrition Sciences, Hospital S. Joao, Porto, Portugal.

Asia Pac J Clin Nutr. 2004; 13(Suppl): S151

Background: Phase angle studied by bioelectrical impedance analysis (BIA) correlates with morbidity and mortality among hemodialysis (HD) patients, and intracellular water (ICW) volume is a reliable surrogate of protein metabolism. While chronic renal failure patients present a significantly disturbed body water composition, no studies have been done on its behaviour following kidney grafting. We report the changes associated with a successful kidney transplant (Tx) on body composition evaluated by BIA, during first months post-surgery. Methods: Twelve Tx patients (7 males, 5 females) were studied. Each patient received triple-drug immuno-suppressive therapy. BIA was assessed before Tx, at month 1 post-Tx and at month 3 post-Tx. Total body water (TBW), extracellular water (ECW), intracellular water (ICW), Na:K exchange rate (Nae:Ke) and phase angle (PA) were studied. An healthy group and a HD group were evaluated three times in a year interval, and HD group was evaluated both before and after a dialysis session. Results: When we compared body composition before Tx with month 1 post-Tx, TBW, ECW and Nae:Ke increased, while ICW and PA decreased significantly. When we compared month 1 with month 3 post-Tx, we observed that ECW decreased, while ICW and PA increased. On comparing month 1 post-Tx with the healthy group, Nae:Ke was greater and PA was lower at month 1; at month 3, only TBW was greater among Tx patients. Conclusions: Our study shows that following successful grafting, kidney transplant recipients reach a new body water composition equilibrium, which is rapidly attained during the first period post-surgery. More importantly, BIA showed that the different body water compartments of kidney transplant recipients quickly match the constitution of normal individuals, overcoming both potential drug therapy side-effects and a suboptimal glomerular filtration as compared to two-kidney healthy controls.

PMID: 15294709 [PubMed - as supplied by publisher]

Body composition assessed by impedance changes very early with declining renal graft function

Coroas A, Oliveira JG, Sampaio S, Borges C, Tavares I, Pestana M, De Almeida MD.

Faculty of Food and Nutrition Sciences, Hospital S. Joao, Porto, Portugal.

Asia Pac J Clin Nutr. 2004; 13(Suppl): S150

Background: Kidney transplant (Tx) restores renal filtration, but it does not achieve the function of two native kidneys, and with time it may slowly involute back to chronic renal failure. We hypothesised that the study of body composition by bioelectrical impedance analysis (BIA) might highlight differences for body compartments among Tx with good, borderline and bad filtration rates. Methods: Thirty Tx patients (19 males, 11 females) were studied at 62.4+/-26.6 months post-surgery and divided into three groups depending on creatinine clearance (crCl): good (crCl > 65.0), borderline (35.0
PMID: 15294708 [PubMed - as supplied by publisher] 

Nutritional status and body composition evolution in early post-renal transplantation - is there a female advantage?

Coroas A, Oliveira JG, Sampaio S, Borges C, Tavares I, Pestana M, De Almeida MD.

Faculty of Food and Nutrition Sciences, Hospital S. Joao, Porto, Portugal.

Asia Pac J Clin Nutr. 2004; 13(Suppl): S150

Background: Chronic renal failure is associated with metabolic derangements, affecting protein, amino acids and lipids, and usually, these patients follow a restricted diet. Kidney transplant (Tx) patients enjoy a recovery of renal function, but their therapeutics may entail significant changes on general metabolism. We present the anthropometrics results during the first three months after successful Tx, for males and females, and we compared them with a healthy group. Methods: Eighteen patients (11 males and 7 females) were studied. Anthropometry was assessed before Tx, at month 1 and at month 3 post-Tx. Body weight (Wt), body mass index (BMI), triceps (TSF), biceps (BSF), subscapular (SCSF) and suprailiac skinfolds (SISF), midarm circumference (MAC), midarm muscle circumference (MAMC), corrected arm muscle area (CT.AMA), total body muscle mass (MM), body density (D), fat-mass (FM) and fat-free mass (FFM) were studied. The healthy group was evaluated three times in a year interval. Results: Pre-Tx, males presented lower Wt, BMI, TSF, BSF, SCSF, SISF, MAC, MAMC, CT.AMA, MM, FM and FFM than controls while females displayed no differences. By the third month, males showed only a partial recovery and females displayed higher TSF and SCSF than controls. Conclusions: Uremic males before Tx displayed undernutrition indexes. During the first three months post-Tx males showed an incomplete recovery of anthropometric parameters. Quite differently, females started at pre-Tx close to normal, but they significantly increased body weight and fat content. We suggest that nutritional requirements post-kidney grafting may be significantly different in males as compared to females.

PMID: 15294707 [PubMed - as supplied by publisher]

Bioimpedance analysis highlights changes in body composition at the early stages of impairment of kidney transplant function

Coroas A, de Oliveira JG, Sampaio S, Borges C, Tavares I, Pestana M, de Almeida MD.

Nephrology Department, S Joao Hospital, Porto, Portugal. jcasimiro@mail.telepac.pt

J Ren Nutr. 2004; 14(3): 157-63

OBJECTIVE: Kidney transplantation restores renal filtration, although it does not achieve the function of 2 native kidneys, and with time it may involute back to chronic renal failure. We hypothesized that bioelectrical impedance analysis (BIA) might highlight differences for body compartments among kidney transplants (Tx) with different filtration rates. METHODS: Thirty transplantation patients (19 male, 11 female) were studied at 62.4+/-26.6 months postsurgery and were divided into 3 groups: good creatinine clearance (crCl, mL/min/1.73 m2; >65.0), borderline (35.0

RESULTS: BIA showed no differences between healthy controls and good Tx, whereas both borderline and bad Tx presented a significantly higher ECW and lower ICW than either good Tx or normal controls. Only good crCl was different from predialysis.

CONCLUSIONS: A good graft kidney manages to restore and maintain normal body composition, whereas with mild renal dysfunction a change in body compartments was observed, moving toward the body water composition of chronic renal failure patients.

PMID: 15232794 [PubMed - in process]

Cyclosporine versus tacrolimus in kidney transplantation: are there differences in nephrotoxicity?

Martins L, Ventura A, Branco A, Carvalho MJ, Henriques AC, Dias L, Sarmento AM, Amil M.

Nephrology Department, Hospital de Santo Antonio, Porto, Portugal. lasalete@clix.pt

Transplant Proc. 2004; 36(4): 877-9

Cyclosporine and tacrolimus, two calcineurin inhibitors, show different side effects and toxicities. The data concerning their nephrotoxicity are few and conflicting. A retrospective study was performed in 2 groups of renal transplant recipients treated with cyclosporine or tacrolimus to evaluate graft function and side effects. All patients had completed at least 6 months of follow-up before inclusion in the study. Group I included 10 patients who were converted from cyclosporine to tacrolimus, due to cosmetic problems or due to chronic graft dysfunction with creatinine values <3 mg/dL. After conversion, there was a significant reduction in creatinine values (from 2.43 +/- 1.21 to 1.86 +/- 0.72 mg/dL; P =.023) and an improvement in creatinine clearance (from 47.5 +/- 19.2 to 56.1 +/- 18.9 mL/min; P =.047). The lipid profile did not change, but there was a trend to better blood pressure control with less antihypertensive drugs.
Group II compared 2 subgroups of patients receiving kidneys from the same donor, one treated with cyclosporine and the other with tacrolimus. Tacrolimus patients showed better renal function; namely, creatinine was 1.15 +/- 0.27 versus 1.44 +/- 0.33 mg/dL (P =.029) and creatinine clearance was 87.7 +/- 27.1 versus 60.3 +/- 25.9 mL/min (P =.043). Lipid and blood pressure values were not different between the 2 subgroups, but tacrolimus patients tended to need a lower number of antihypertensive medications. The incidence of de novo diabetes mellitus was approximately 20% among patients using tacrolimus. We concluded that tacrolimus may be less nephrotoxic than cyclosporine. Tacrolimus patients showed better graft function and easier blood pressure control, but a high incidence of posttransplantation diabetes mellitus.

PMID: 15194300 [PubMed - in process] 

Early cyclosporine a withdrawal in kidney-transplant recipients receiving sirolimus prevents progression of chronic pathologic allograft lesions

Ruiz JC, Campistol JM, Grinyo JM, Mota A, Prats D, Gutierrez JA, Henriques AC, Pinto JR, Garcia J, Morales JM, Gomez JM, Arias M.

Hospital Universitario Marques de Valdecilla, Santander, Spain.

Transplantation. 2004; 78(9): 1312-8

BACKGROUND: Nephrotoxicity of calcineurin inhibitors (CNIs) is partially responsible for the development of chronic allograft nephropathy (CAN). Sirolimus has demonstrated its potential to substitute for CNIs because it lacks significant nephrotoxicity and shows a short-term immunosuppressive capacity comparable with that of cyclosporine. This results in the maintenance of better renal function when cyclosporine is eliminated, but it has not been demonstrated whether this benefit is associated with an improvement in the pathologicsubstrate and a reduction in CAN. METHODS: We analyzed pretransplant and 1-year renal-allograft biopsies from 64 patients enrolled in a multicenter trial. Patients received cyclosporine and sirolimus during the first 3 months after transplant and were then randomly assigned to continue with cyclosporine or have it withdrawn. Histologic chronic allograft lesions were compared between groups. RESULTS: The percentage of patients in whom chronic pathologic lesions progressed was lower in the group of cyclosporine elimination. Significant differences were observed in chronic interstitial and tubular lesions (70% vs. 40.9% [P<0.05] and 70% vs. 47.8% [P<0.05], respectively), whereas no differences were observed in acute lesions (subclinical rejection). Prevalence of CAN at 1 year was lower in this group, as was the severity and incidence of new cases (P<0.05). CONCLUSIONS: Early cyclosporine withdrawal associated with sirolimus administration is followed by an improvement in renal function, a reduction in the progression of chronic pathologic allograft lesions, and a lower incidence of new cases and severity of CAN during the first year after transplantation. This benefit may result in better long-term graft outcome.

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 15548969 [PubMed - indexed for MEDLINE]

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