Differences in the renal dopaminergic system activity between Wistar rats from two suppliers
Institute of Pharmacology and Therapeutics, University of Porto, Portugal.
Acta Physiol Scand. 2003; 178(1): 83-9
AIM: Dopamine of renal origin reduces tubular sodium reabsorption and controls blood pressure. The present study evaluated renal dopaminergic activity and its response to uninephrectomy in Wistar Han rats from two suppliers, Harlan (W-H) and Charles River (W-CR). RESULTS: After uninephrectomy, the fractional excretion of sodium (FENa+) increased in both W-CR and W-H rats (W-CR: from 0.17 +/- 0.01 to 0.27 +/- 0.02%; W-H: from 0.39 +/- 0.04 to 0.54 +/- 0.04%, P < 0.05); however, in W-CR rats the FENa+ was lower than in W-H rats in both Sham and uninephrectomized (Unx) animals (P < 0.05). Systolic blood pressure in Unx W-CR rats was higher than in Unx W-H animals (131 +/- 3 vs. 122 +/- 2 mmHg, P < 0.05). Uninephrectomy was accompanied in W-H rats by increases in urinary levels (nmol g kidney(-1) day(-1)) of dopamine (10.3 +/- 0.5 vs. 8.3 +/- 0.7, P < 0.05) and 3,4-dihydroxyphenylacetic acid (DOPAC) (30.5 +/- 3.7 vs. 21.3 +/- 1.4, P < 0.05) and increases (P < 0.05) in maximal velocity values (Vmax in nmol mg prot(-1) 15 min(-1), 325 +/- 12 vs. 265 +/- 3) for renal aromatic L-amino acid decarboxylase (AADC), the enzyme responsible for the synthesis of renal dopamine. By contrast, in W-CR rats uninephrectomy did not change either the urinary levels of dopamine (7.1 +/- 0.5 vs. 7.6 +/- 0.7) and DOPAC (25.0 +/- 1.9 vs. 24.8 +/- 4.1) or AADC activity (Vmax 199 +/- 3 vs. 193 +/- 9). The Vmax values for renal AADC in W-CR rats were lower than those found in corresponding W-H animals. CONCLUSION: Wistar rats from different suppliers represent an important source of variability in the renal dopaminergic system activity. This may contribute to differences in sodium balance and blood pressure control in response to uninephrectomy.
PMID: 12713518 [PubMed - indexed for MEDLINE]
Peritoneal Dialysis Today, Contributions to Nephrology, Editors: C Ronco, R dell’Aquila, M P Rodidhiero, vol 140,2003:195-201.
The right management of the access is a key factor for the improvement of PD technique survival. A great variability of catheters and protocols has been used with efficacy but there is few level A evidence studies to prove the superiority of any of them. Each Centre should have a dedicated team (nephrologist, surgeon and nurses) with experience and skill, who accurately observes and analyses the results of their methodology and timely treats complications. This proves to be more important than either the type of catheter or implantation methodology to achieve best results. Prophylaxis with topic mupirocine is under debate but proved to be efficient to reduce St. aureus infections. Recent technological advances such as laparoscopy and radiological manipulations promise further improvements in access management.
Techniques of peritoneal catheter insertion
Hemodialysis vascular access and peritoneal dialysis access. Contributions to Nephrology.Editors C Ronco, NW Levin, vol 142, 2003: 402-409
To optimize peritoneal dialysis technique major efforts have been done with new catheter designs and connecting devices. But operative technique is probably a stronger determinant of successful catheter function.
A centre effect is a remarkable confounding factor when analysing different implantation protocols. Blind percutaneous catheter placement allows in some Centres similar catheter survival when compared to surgical procedure but it implies a higher risk of bowel perforation. Minilaparotomy is a safer method and if performed with experience and skill assures low rate of leak and infectious complications. It should be performed under local anaesthesia, in an out-patient procedure, unless the patient is a candidate to simultaneous correction of adhesions or hernias or unable to cooperate with local anaesthesia. Peritoneoscopy using a 2 mm Y-TEC assures excellent results in experienced hands, but it isn’t consistently superior to minilaparotomy. Selected patients with suspected adhesions might be preferably managed with peritoneoscopic catheter implantation. Laparoscopy however has a definite advantage if simultaneous correction of intrabdominal complications is needed or in case of replacement of dysfunctional catheters.
Whichever the method used, the success on catheter management is mainly depending on the commitment and skill of the operator and team care (surgeon, nephrologist, PD nurse). Monitoring and control of the complication rate is mandatory in order to optimize peritoneal catheter implantation.
Conduite à tenir en cas d?hiperpermeabilite péritonéal
Le Bulletin de la Dialyse Peritoneale 2003; 12(2): 27-33
L’approche thérapeutique chez les patients ayant une membrane péritonéale hyperperméable doit tenir compte du fait qu’il s’agit d’un groupe hétérogène. Différentes conditions, une inflammation soit systématique soit locale, des modifications anatomiques ou fonctionnelles, des promoteurs pathologiques ou physiologiques peuvent être impliqués. L’évolution la plus favorable semble concerner les patients ayant une hyperperméabilité péritonéale précoce au début de la DP qui peut être la conséquence d’une masse mésothéliale importante produisant des taux élevés de VEGF. Des études préliminaires sont en faveur de cette hypothèse mais ces résultats demandent à être validés. Une évolution moins favorable des cas d’hyperperméabilité péritonéale se voit en cas de comorbidités sévères et de MIA syndrome. Toute intervention devra faire face à des situations encore incomplètement connues, faisant intervenir les cytokines pro-inflammatoires, l’urémie, les métabolites des AGE et du NO. En cas d’hyperperméabilité acquise, même avec une perte sévère d’ultrafiltration, une intervention adéquate et en temps peut améliorer le devenir de ces patients. Une stratégie préventive doit inclure la protection de la fonction rénale résiduelle et éviter l’exposition excessive aux produits de dégradation du glucose. L’objectif thérapeutique immédiat sera d’assurer un contrôle volémique satisfaisant. Le succès dépendra du caractère réversible des lésions existantes.
Familial ATTR amyloidosis: microalbuminuria as a predictor of symptomatic disease and clinical nephropathy
|Luísa Lobato1,2,3, Idalina Beirão1,3, Manuela Silva1, Fernanda Bravo4, Frederico Silvestre5, Serafim Guimarães1, Alda Sousa2,3,6, Laure-Hélène Noël7 and Jorge Sequeiros2|
1 - Department of Nephrology, Hospital Geral de Santo António, Porto
2 - Institute for Molecular and Cell Biology, Porto
3 - Centro de Estudos de Paramiloidose, Porto
4 - Department of Clinical Pathology, Hospital Geral de Santo António, Porto
5 - Department of Pathology, Hospital Geral de Santo António, Porto
6 - Department of Population Studies, ICBAS, Universidade do Porto, Portugal
7 - Service de Nephrologie, Hôpital Necker, Paris, France
Nephrol Dial Transplant 2003; 18: 532-538
Background. Portuguese type familial amyloid polyneuropathy (FAP) is a neuropathic amyloidosis caused by a mutant transthyretin (TTR). Varying degrees of renal involvement have been reported. Our aim was to assess the value of microalbuminuria (MA) for predicting clinical neurological disease and overt nephropathy in TTR-related amyloidosis.
Methods. All subjects had the TTR Val30Met mutation, and were recruited between 1993 and 1999. We have prospectively evaluated 22 asymptomatic gene carriers (7 male, 15 female; mean age 41.6"9.6 years) and 32 patients with neuropathy (14 male, 18 female; 36.8"8.8 years, on average, 33.0"9.3 years at the onset of neuropathy). We measured urinary albumin excretion every year, if asymptomatic, or every 6 months if already affected. Kidney biopsies were performed in patients with normal urinary albumin excretion, MA, and overt nephropathy, respectively.
Results. In asymptomatic carriers, persistent MA was detected in eight (36%) subjects. The presence of MA in asymptomatic gene carriers, compared with those having normal urinary albumin excretion, conferred
a 4.8-fold risk of developing neuropathy, usually within the subsequent 3 years. Once neurological signs appeared, nephropathy, manifested as MA, progressed to overt nephropathy in one-half of subjects. In patients with neuropathy, 24 (75%) had MA during follow-up: evolution towards clinical renal disease occurred in 14 (58%) and renal failure occurred in five (21%), always after a course of MA. Proteinuria or renal failure without prior persistent MA were never observed in the present patient cohort. Histopathological evaluation did not reveal glomerular lesions other than amyloid deposits to explain abnormal urinary albumin excretion. The amount of mesangial and vascular-pole amyloid deposits was correlated
with the degree of albuminuria.
Conclusions. Microalbuminuria represents the first stage of clinical TTR amyloid nephropathy and is premonitory of neuropathy. Its presence identifies a subgroup of patients who are more prone to develop overt nephropathy. Screening of MA may be important to assess disease onset and to recommend liver transplantation in individuals at risk.
Portuguese-type amyloidosis (transthyretin amyloidosis, ATTR V30M)
Department of Nephrology, Santo Antonio General Hospital, Porto, Portugal. email@example.com
J Nephrol. 2003; 16(3): 438-42
Rinherited in autosomal dominant mode. The disease, also called familial amyloid polyneuropathy type I (FAP-I), is caused by a mutant transthyretin (TTR) protein, which is synthesized by the liver. A single amino acid substitution of methionine for valine at position 30 of the TTR molecule (TTR V30M) was found in Portuguese patients. The clinical disease usually manifests as a peripheral sensory, motor and autonomic neuropathy starting in the 3rd or 4th decade of life. Renal manifestations of ATTR V30M, like other amyloidoses, are different levels of proteinuria and renal insufficiency. In ATTR V30M a large amyloid deposition in the medullary zone of the kidney and tubules is characteristic. A more extensive glomerular and vascular involvement is present only in patients with renal manifestations. A prospective survey in the north of Portugal showed that a stage of microalbuminuria (MA) could precede nephropathy and neurological disease. Nephropathy in FAP-I is present in one-third of affected patients and tends to aggregate in families. The progression towards end-stage renal disease (ESRD) affects 10% of the patients, and the survival after initiation of dialysis is a mean of 21 months. Patients who progress to ESRD have a late onset of neuropathy and lower prevalence of clinical disease in their families. Liver transplantation is a widely accepted treatment for FAP-I, and combined liver-kidney transplantation is also an option for selected patients with FAP-I and ESRD.
PMID: 12832749 [PubMed - indexed for MEDLINE]
Calcimimetic Agents: Review and perspectives
|Pablo Ureña* and João M. Frazão**|
*Service de Néphrologie et Dialyse. Clinique de l’Orangerie, Aubervilliers. France and
** Department of Nephrology, Hospital São João, Porto, Portugal
School of Medicine, University of Porto, Portugal
Ureña P, Frazão JM. Calcimimetic Agents: Review and Perspectives. Kidney Int 2003; 63(Suppl.85): S91-S96
Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The activation of this receptor by small changes in the extracellular ionized calcium (ec(Ca2+)) regulates PTH, calcitonin secretion, urinary calcium excretion and ultimately bone turnover. The cloning of this CaR and the discovery of mutations making the receptor less or more sensitive to calcium allowed a better understanding of several hereditary disorders characterized either by hyperparathyroidism or hypoparathyroidism. This CaR became an ideal target for the development of compounds, the calcimimetics, able to amplify the sensitivity of the CaR to Ca ++ suppressing PTH levels with a resultant fall in blood Ca++. Experiences with R-568 in patients with primary and secondary hyperparathyroidism and parathyroid carcinoma are summarized. The first clinical studies with the first-generation calcimimetic agents have demonstrated their efficacy lowering plasma intact PTH concentration in uremic patients with secondary hyperparathyroidism. However, the low bioavailability of these first calcimimetics predict a difficult clinical utilization. The second generation calcimimetic, AMG 073, with a better pharmacokinetic profile appears to be effective and safe for the treatment of secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia and increased calcium X phosphorus product is very promising.
Physical examination versus normalized pressure ratio for predicting outcomes of hemodialysis access interventions
|Trerotola SO, Ponce P, Stavropoulos SW, Clark TW, Tuite CM, Mondschein JI, Shlansky-Goldberg R, Freiman DB, Patel AA, Soulen MC, Cohen R, Wasserstein A, Chittams JL.|
Department of Radiology, Division of Interventional Radiology, University of Pennsylvania Medical Center, Philadelphia 19104, USA. firstname.lastname@example.org
J Vasc Interv Radiol. 2003; 14(11): 1387-94
PURPOSE: The ratio of intragraft venous limb pressure (VLP) to systemic pressure (S) has been proposed to help determine the endpoint of hemodialysis access interventions. It was hypothesized that physical examination of the access could be used in the same way and these techniques were compared as predictors of outcome. PATIENTS AND METHODS: With use of a quality-assurance database, records from 117 hemodialysis access interventions were retrospectively reviewed. Only interventions in grafts were included. The database included physical examination (to establish thrill, thrill with slight pulsatility [TSP], pulse with slight thrill [PST], and pulse) at three locations along the graft (proximal, midportion, and distal), normalized pressure ratio calculated with S from a blood pressure cuff (S(cuff)) and S within the graft with outflow occluded (S(direct)), graft configuration and location, indication, operator, and time to next intervention (outcome of primary patency). Only procedures with complete follow-up data were included in the analysis (n = 97; declotting, n = 51; prophylactic percutaneous transluminal angioplasty [PTA], n = 46). Statistical analysis was performed with use of Cox proportional-hazards regression. RESULTS: Graft configuration, location, side, VLP, S(direct), and S(cuff) did not affect outcomes. An operator effect was noted for two physicians and was adjusted for in all analyses. Pressure ratios were weak predictors of outcome (VLP/S(direct), P =.07; VLP/S(cuff), P =.08) and suggested that patency increased with increasing pressure ratio, contrary to earlier studies. Procedure type predicted outcome (declotting, median patency of 50 days; PTA, median patency of 105 days; P =.01). Thrill at distal physical examination was predictive of outcome (P =.04) and even more so when thrill and TSP combined were compared with PST and pulse combined (P =.03). Similar but less-pronounced effects were seen at midportion and proximal physical examinations. CONCLUSIONS: The presence of a thrill or slightly pulsatile thrill at the distal (venous) end of a dialysis graft is the best predictor of outcome after percutaneous intervention. Based on the present study, the authors believe that physical examination of dialysis access should supplant pressure measurements as an endpoint of intervention and should serve as an essential component of quality assurance of access interventions.
PMID: 14605103 [PubMed - indexed for MEDLINE]
End-stage renal disease in familial amyloidosis ATTR Val30Met: a definitive indication to combined liver-kidney transplantation
Department of Nephrology, and Liver Transplantation Program, Hospital Geral de Santo Antonio, Largo Professor Abel Salazar, 4050, Porto, Portugal. email@example.com
Transplant Proc. 2003; 35(3): 1116-20
Homocysteine levels in pediatric renal transplant recipients
Department of Paediatric Nephrology, Maria Pia Children's Hospital, R. da Boavista, 827, 4050-111, Porto, Portugal. firstname.lastname@example.org
Transplant Proc. 2003; 35(3): 1093-5
PMID: 12947872 [PubMed - indexed for MEDLINE]
Long-term improvement in renal function with sirolimus after early cyclosporine withdrawal in renal transplant recipients: 2-year results of the Rapamune Maintenance Regimen Study
Innere Medizin III-Nephrologie, Allgemeines Krankenhaus, Vienna, Austria. email@example.com
Transplantation. 2003; 76(2): 364-70
INTRODUCTION: The purpose of this study was to evaluate early cyclosporine (CsA) withdrawal from a sirolimus (SRL)-CsA-steroid (ST) regimen. METHODS: Within 48 hr after transplantation, 525 primary (90%) or secondary (10%) renal allograft recipients with cadaveric (89%) or living (11%) donors received 2 mg of SRL (troughs >5 ng/mL; immunoassay), CsA, and ST. Those eligible (430) were randomly assigned (1:1) at 3 months +/- 2 weeks to remain on triple-drug therapy (SRL-CsA-ST group) or to have CsA withdrawn and SRL trough concentrations targeted to 20 to 30 ng/mL (SRL-ST group) until month 12, and 15 to 25 ng/mL thereafter. RESULTS: At 24 months, there were no statistically significant differences in patient survival (94.0% vs. 95.3%), graft survival (91.2% vs. 93.5%), acute rejection after randomization (5.1% vs. 9.8%) or discontinuations (34% vs. 33%) for SRL-CsA-ST versus SRL-ST, respectively. Serum creatinine level was significantly better in patients who had CsA withdrawn (167 vs. 128 micromol/L, P<0.001), as was the slope of 1/creatinine. Similarly, systolic blood pressure was lower in patients who had CsA withdrawn (141 vs. 134 mm Hg, P<0.001). High-density lipoprotein cholesterol was significantly higher in the SRL-ST group, whereas total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were not significantly different. Hypertension, creatinine increase, abnormal kidney function, toxic nephropathy, edema, hyperuricemia, cataracts, Herpes zoster, and malignancy were reported significantly more often in patients continuing CsA. Thrombocytopenia, hypokalemia, abnormal liver function tests, abnormal wound healing, ileus, and pneumonia were reported significantly more frequently with SRL-ST. CONCLUSION: Data at 2 years confirm that early CsA withdrawal followed by an SRL-ST maintenance regimen results in long-term improvement in both renal function and blood pressure, without increased risk of graft loss or late acute rejection.
Randomized Controlled Trial
PMID: 12883194 [PubMed - indexed for MEDLINE]