Miguel Pérez Fontán

Hyperleptinemia in uremic patients undergoing conservative management, peritoneal dialysis, and hemodialysis: A comparative analysis

We performed a cross-sectional study in a wide sample of patients with chronic renal failure undergoing conservative therapy (CTh) (n = 79), peritoneal dialysis (PD) (n = 75), and hemodialysis (HD) (n = 51), with the aim of analyzing the impact of the different modes of therapy on serum leptin levels. We used a multivariate approach, taking into consideration the potential effects of other epidemiological, dialysis-related, nutritional, and hormonal factors on serum leptin. Leptin levels were higher in patients treated with PD (median, 36 ng/mL) than in those undergoing CTh (10.8 ng/mL) or HD (5.4 ng/mL) (P < 0.0005). This difference persisted after controlling for gender, body mass index, and fasting insulin levels, suggesting that imbalances in these factors may only partially explain the differences found between the three modes of therapy. Leptin levels showed a significant negative correlation with peritoneal protein losses in PD patients but were poorly associated with factors such as proteinuria, daily peritoneal glucose absorption (PD), renal function, or adequacy of dialysis. Leptin and insulin-like growth factor-I (IGF-I) were significantly correlated in PD patients, but the study design did not allow for establishing a meaning for this correlation. In conclusion, serum leptin levels are increased in PD patients when compared with CTh or HD patients. Differences in gender distribution, fat mass, and insulin levels may partially explain these findings, but other undefined factors also may have a role in producing these results.

EARLY PROTEINURIA IN RENAL TRANSPLANT RECIPIENTS TREATED WITH CYCLOSPORIN

PURPOSE To establish the risk profile for the development of proteinuria in the first months after renal transplantation and to disclose the prognostic significance of this finding. DESIGN We conducted an observational historic cohort study. SETTING We conducted the study in a tertiary care hospital renal transplantation unit covering a potential population of approximately 2 million. We made extensive use of suboptimal donors. POPULATION In our unit, 560 cadaveric renal transplants were performed between January 1988 and June 1997, under Cyclosporine immunosuppression, with a minimum follow up of 1 year. METHOD The risk profile analysis explored early clinical factors reported to be related to the late course of renal transplantation. The study of the prognostic significance of proteinuria included survival analysis and correlation with late markers of graft dysfunction, taking into consideration the intensity and persistence of early proteinuria. A multivariate approach was used in all cases. RESULTS Early proteinuria was strongly associated with delayed graft function (odds ratio [OR] 1.03/day of dialysis), acute rejection (OR 1.7 for steroid-sensitive and 6.2 for steroid-resistant rejection), renal transplant to a hypersensitized recipient (OR 2.5), and pediatric (<5 years)(OR 4.1) or older (>60 years)(OR 3.0) donors. The predictive model for persistency of proteinuria was very similar, whereas transient proteinuria could not be adequately modeled. Increasing intensity of proteinuria was strongly associated with poor patient and graft survival. Persistent, but not transient, proteinuria supported this relationship. CONCLUSIONS Proteinuria appearing early after renal transplantation is strongly associated with delayed graft function, acute rejection, and the use of pediatric or older donors. Whatever its background, proteinuria is a strong predictor of poor patient and graft survival. This effect is directly related to the intensity and persistence of the disorder.

Early immunologic and nonimmunologic predictors of arterial hypertension after renal transplantation

We followed up a cohort of 680 renal transplant recipients receiving cyclosporine (CsA) immunosuppression with the aim of establishing an early-risk profile for early and late hypertension (HT) after renal transplantation (RTx), specifically comparing the predictive role of immunologic and nonimmunologic markers of graft prognosis. HT was defined as the need for antihypertensive drugs. The prevalence of HT was 65% at the time of RTx, increased to a peak of 78% at the end of the first year, and stabilized between 71% and 73% thereafter. Multivariate analysis identified HT at the time of RTx, basal renal disease, and grafting the right kidney as independent predictors of HT 3 months after RTx. The risk profile for HT 12 months after RTx included HT present at RTx, grafting the right kidney, markers of early ischemia-reperfusion injury (delayed graft function, cold and warm ischemia), and transplant from an elderly or female donor. Polytransfusion before RTx was associated with a decreased risk for HT, but retransplantation, increased reactivity against the lymphocyte panel, poor HLA compatibility, and early acute rejection did not portend an increased risk for the complication under study. The CsA schedule (dose, trough levels) correlated poorly with the blood pressure status of the patients, but simultaneous graft function was independently associated with late HT. In conclusion, the early predictive profile for HT after RTx includes, preferentially, nonimmunologic markers of graft prognosis. Hyperfiltration damage may be a significant pathogenic mechanism for this complication of RTx.

Hyperleptinemia is not correlated with markers of protein malnutrition in chronic renal failure: A cross-sectional study in predialysis, peritoneal dialysis and hemodialysis patients

Background: Serum leptin levels are increased in chronic renal failure (CRF) and may potentially contribute to protein malnutrition in this disorder. Method: Following a cross-sectional design, we performed a nutritional survey in a wide sample of uremic patients treated conservatively (n = 87), with peritoneal dialysis (n = 71) and with hemodialysis (n = 53). Then, we analyzed the correlation between serum leptin levels and markers of protein malnutrition. We used a multivariate approach, taking into consideration the confounding effect of other factors on the correlation between hyperleptinemia and protein malnutrition. Main Results: Both univariate and multivariate analysis disclosed a poor correlation between hyperleptinemia and markers of protein malnutrition. In fact, there were trends to a positive correlation between leptinemia and body protein stores, as estimated from the scrutinized markers. Persistence of the basic correlation between general intake, fat mass and leptin in CRF could partially explain these findings, but neither a negative correlation between leptin levels nor protein nutritional state could be disclosed after controlling for this factor. Conclusions: Our results do not support a first-line role for hyperleptinemia in the genesis of protein malnutrition of uremia.

Chylous ascites associated with acute pancreatitis in a patient undergoing continuous ambulatory peritoneal dialysis

We report on a case of chylous ascites associated with acute pancreatitis secondary to gallbladder stone disease, in a patient undergoing continuous ambulatory peritoneal dialysis. The initial clinical presentation was one of bacterial peritonitis, with later appearance of chylous peritoneal drainage. Diagnosis was suggested by abdominal computed tomography and confirmed by surgical exploration. We discuss the main diagnostic keys of peritoneal dialysis-associated pancreatitis and the possible etiologic role of this entity in chylous ascites of these patients.

Categorization of sodium sieving by 2.27% and 3.86% peritoneal equilibration tests—a comparative analysis in the clinical setting

BACKGROUND Analysis of the dialysate sodium concentration during a peritoneal equilibration test (PET) provides information on the rates of water and solute transport through different membrane pathways. A hypertonic (3.86%) glucose-based dialysate may enhance the accuracy of analysis. There are still gaps in our knowledge regarding this question, in the clinical setting. Objective. The aim of this study was to compare the categorization of the sodium sieving effect in peritoneal dialysis (PD) patients by 2.27% and 3.86% PETs, and to disclose clinical correlates of this phenomenon. Method. Ninety PD patients underwent prospectively 2.27% and 3.86% modified (dialysate samples at 0, 60, 90, 120 and 240 min) PETs, in a random order. We searched for differences in the time profiles of sodium sieving and its categorization. We correlated sodium sieving with ultrafiltration (UF) and solute transport capacity, as also with selected clinical and demographic variables, using a multivariate approach. RESULTS The maximum dip in the dialysate sodium concentration (11.1 mM/L, 3.86% versus 7.1 mM/L, 2.27%, P < 0.001) was most common after 90 min in the 3.86% PET, with the 2.27% test somewhere between 60 and 90 min. Low sodium sieving (defined by a dip <5 mM/L at 60 min) was observed in 8.9% of the patients in the 3.86% test. The same limit categorized 34.4% of the patients as low sieving in the 2.27% test (100.0% sensitivity and 72.0% specificity, using 3.86% as a reference). UF and D/P(240 min) creatinine were independent predictors of the sodium sieving effect in both tests. Moreover, multivariate analysis disclosed a consistent inverse correlation between GFR and sodium sieving in both the 2.27% (B = -0.23, 95% CI -0.40, -0.07, P = 0.006) and 3.86% PET (B = -0.46, 95% CI -0.65, -0.26, P < 0.0005). CONCLUSIONS The standard 2.27% PET permits some categorization of sodium sieving in PD patients. However, the information provided by this test lacks the discriminatory capacity of the 3.86% PET, which should be considered the one for reference for this purpose. GFR keeps a consistent inverse correlation with the intensity of sodium sieving in both the 2.27% and 3.86% PET.

Getting the Right Patient on the Right Renal Replacement Therapy

Adequate selection of the modality of renal replacement therapy (RRT), ideally based on well-planned predialysis care, informed decision by the patient and timely initiation of dialysis, is essential to optimize the outcome of patients with chronic kidney disease. However, there are important practical limitations to the success of this process. A major consequence is the underutilization of home-based dialysis therapies, including peritoneal dialysis (PD). A wide array of medical and social factors have been invoked as contraindications to PD, but well-designed studies have shown that most patients (probably >70%) starting dialysis are suitable for this technique. PD is feasible and may be preferred by a significant proportion of patients in many claimed unfavorable settings. The practicing nephrologist should be able to: disclose which are insurmountable barriers to PD, clarify the significance of relative contraindications in individual cases, and identify favorable and unfavorable settings for home dialysis. These abilities will permit quality education, justified advice, well-targeted informed decision and, predictably, successful selection of the modality of RRT. This article provides some clues to approach these issues in three different settings: planned start of RRT after predialysis care, unplanned start of dialysis and programmed changes of modality during follow-up.

Effect of self-administered intraperitoneal bemiparin on peritoneal transport and ultrafiltration capacity in peritoneal dialysis patients with membrane dysfunction. A randomized, multi-centre open clinical trial

BACKGROUND Progressive peritoneal membrane injury and dysfunction are feared repercussions of peritoneal dialysis (PD), and may compromise the long-term feasibility of this therapy. Different strategies have been attempted to prevent or reverse this complication with limited success. METHODS We performed a randomized, open multi-centre trial, aimed at scrutinizing the efficacy of self-administered intraperitoneal (i.p.) bemiparin (BM) to modulate peritoneal membrane dysfunction. The main outcome variables were peritoneal creatinine transport and the ultrafiltration (UF) capacity, estimated during consecutive peritoneal equilibration tests. The trial included a control group who did not undergo intervention. The treatment phase lasted 16 weeks with a post-study follow-up of 8 weeks. RESULTS Intraperitoneal BM did not significantly improve creatinine transport or the UF capacity, when the whole group was considered. However, we observed a time-limited improvement in the UF capacity for the subgroup of patients with overt UF failure, which was not observed in the control group. Intraperitoneal injection of BM did not carry an increased risk of peritoneal infection or major haemorrhagic complications. CONCLUSIONS Our data do not support the systematic use of BM for management of peritoneal membrane dysfunction in PD patients. Further studies on the usefulness of this approach in patients with overt UF failure are warranted. Intraperitoneal administration of BM is safe in PD patients, provided regulated procedures are respected.

Analysis of Ultrafiltration Failure Diagnosed at the Initiation of Peritoneal Dialysis with the Help of Peritoneal Equilibration Tests with Complete Drainage at Sixty Minutes. A Longitudinal Study.

♦ Background: Ultrafiltration failure (UFF) diagnosed at the initiation of peritoneal dialysis (PD) has been insufficiently characterized. In particular, few longitudinal studies have analyzed the time course of water transport in patients with this complication. ♦ Objective: To investigate the time course of peritoneal water transport during the first year on PD in patients presenting UFF since the initiation of this therapy (study group). ♦ Method: Prospective, observational, single-center design. We analyzed, at baseline and after 1 year of follow-up, peritoneal water transport in 19 patients incident on PD with UFF. We used incident patients without UFF as a control group. Water transport was characterized with the help of 3.86/4.25% dextrose-based peritoneal equilibration tests (PETs) with complete drainage at 60 minutes. ♦ Results: The study group revealed a disorder of water transport affecting both small-pore ultrafiltration (SPUF) (p = 0.054 vs incident without UFF) and free water transport (FWT) (p = 0.001). After 1 year of follow-up, FWT displayed a general increasing trend in the study group (mean variation 48.9 mL, 95% confidence interval [CI] 15.5, 82.2, p = 0.012), while the behavior of SPUF was less predictable (−4.8 mL, 95% CI −61.4, 71.1, p = 0.85). These changes were not observed in incident patients without UFF. Neither initial clinical characteristics, baseline PET-derived parameters, or suffering peritoneal infections during the first year predicted the time course of the capacity of UF in the study group. Recovery from incident UFF was apparently linked to improvement of SPUF. ♦ Conclusions: Patients with UFF at the start of PD suffer a disorder of peritoneal water transport affecting both FWT and SPUF. Free water transport increases systematically in these patients after 1 year of follow-up. The evolution of SPUF is less predictable, and improvement of this parameter marks reversibility of this complication.

Low Serum Levels of Vitamin D are Associated with Progression of Subclinical Atherosclerotic Vascular Disease in Peritoneal Dialysis Patients: A Prospective, Multicenter Study

Background: The prevalence of subclinical atherosclerosis and the main predictors of progression of this condition in patients undergoing peritoneal dialysis (PD) have been insufficiently investigated. Objectives and Method: Following a prospective, multicenter, observational design, we studied 237 patients who were treated with PD for ≥3 months, without any clinical background of cardiovascular (CV) disease. Our objectives were the following: (1) to investigate the prevalence of subclinical atherosclerosis, as compared to a control group of age- and sex-matched healthy individuals, and (2) to disclose PD technique-related predictors of progression of disease during a 24-month follow-up period. We used vascular ultrasound for characterization of subclinical atherosclerotic disease. Main Results: A total of 123 patients (51.9%) vs. 79 controls (33.5%) presented ≥1 carotid plaque, and 114 patients (48.3%) vs. 72 controls (30.5%) ≥1 femoral plaque, at baseline evaluation (p < 0.0005). Progression of disease, either in clinical or ultrasound (new plaques) terms, affected 62.6% of patients. Multivariate analysis identified age, carotid intima-media thickness, presence of ≥1 carotid plaque, and serum levels of 25OH vitamin D and C-reactive protein (CRP) at baseline as independent correlates of progression of atherosclerotic disease. On the contrary, PD technique-related variables did not show any association with this outcome. Conclusions: Atherosclerotic vascular disease is frequent among asymptomatic patients undergoing PD. Older age, pre-existent disease (assessed by vascular ultrasound), and serum levels of 25OH vitamin D and CRP are independent markers of the progression of this condition. These findings may contribute to improve identification of subpopulations with a high risk of CV events, deserving intensified measures of prevention.