Plasma adiponectin levels in chronic kidney disease patients: relation with molecular inflammatory profile and metabolic status.

BACKGROUND AND AIM: Adiponectin (ADPN) exerts anti-inflammatory and cardio protective effects and is associated with decreased cardiovascular risk, however its role in patients with chronic kidney disease is unclear. METHODS AND RESULTS: We investigated the correlation between plasma ADPN levels, the progression of CVD and CKD and the inflammatory gene expression profile of peripheral blood mononuclear cells in patients from the NephroPLIC study (a prospective study aimed at addressing the progression of cardiovascular damage in relation to kidney dysfunction). Plasma ADPN levels were directly correlated with age, HDL-C and creatinine, and inversely with BMI, triglycerides and glomerular filtration rate (GFR). Multiple regression analysis identified plasma creatinine and HDL as the independent factors associated with ADPN plasma levels. In peripheral blood mononuclear cells (PBMC), the mRNA expression of MCP-1, CD40, Cox-2, TLR4, PAI-1, TNF alpha, resistin and RAGE was up-regulated in the group with higher GFR and higher ADPN plasma levels compared to that with low GFR and ADPN plasma levels. Patients with similar GFR values showed no differences in the gene expression profile of PBMC although ADPN levels were associated with decreased CRP and IL-6 plasma levels and decreased IMT and heart left ventricular mass. CONCLUSION: In CKD patients who are not in dialysis ADPN plasma levels are associated with a reduced renal excretory function, but correlate inversely with the determinants of the metabolic syndrome such as glucose, triglycerides and BMI, and directly with HDL. Furthermore, in patients with a similar degree of renal impairment, ADPN plasma levels are associated with a better cardiometabolic profile, despite no significant difference being observed in the gene expression pattern of PBMC.

[Census of the Italian Nephrology and Dialysis Units. Comparison between Lombardy and Piedmont]. / Censimento 2004 Centri di Nefrologia e Dialisi. Confronto tra Piemonte e Lombardia.

The Italian Society of Nephrology promoted a national survey to obtain detailed information from all the Renal and/or Dialysis Units through an on-line questionnaire concerning structural, technological and human resources, as well as organisation characteristics and activities. The purpose of this initiative was to obtain regional reference benchmarks for each Nephrology Unit. In this paper we compare two northwestern Italian Regions: Lombardy and Piedmont. As far as epidemiology is concerned, the prevalence of dialysis patients is quite similar in the two Regions: for haemodialysis 616 pmp (patients per million population) in Lombardy and 595 in Piedmont, for peritoneal dialysis 104 pmp vs. 114 pmp, while the incidence of dialysis patients is 169 vs. 166 pmp. The gross mortality for dialysis patients is 12.4% vs. 13.7% and 0.9% vs. 2.0% in transplanted patients. The distribution of vascular access is also quite similar in the two Regions: prevalent arteriovenous fistula 83% vs. 74%, central venous catheter 11% vs. 18%, vascular grafts 7% vs. 8%. Structural resources: the hospital beds (49 pmp in the two Regions) and the dialysis places (161 vs. 166 pmp) do not differ between the two Regions. Personnel resources: physicians 37 pmp in Lombardy and 44 pmp in Piedmont, renal nurses 167 pmp vs. 186, respectively. Activity: hospital admission 1722 pmp vs. 1507 pmp, renal biopsies 131 pmp vs. 109 pmp. Although the two regions examined are numerically different, both have a high standard of quality, making Italy a model of nephrology organisation. This initiative to take a census of the Italian Nephrology and Dialysis Units provides an interesting tool to describe the present status of the operational structures, to identify precise benchmarking values, at both the regional and national level, and to act as a prelude for further rationalization and growth of the nephrology network in Italy.

[Early therapeutic education in chronic renal disease: a new approach]. / La presa in carico precoce nell'insufficienza renale cronica: un nuovo approccio.

Chronic renal failure (CRF) remains a significant problem. Early referral of patients reduces cardiovascular risk and allows better quality of life and life expectancy. Uremic patients represent a typical example of chronic disease, which requires multidisciplinary team involvement and stratification of treatment processes. During the evolution of the disease to chronicity, the patient requires different clinical approaches that form part of a unique treatment process, involving day-to-day management, carried out by the general practitioner, as well as the handling of acute events requiring specialized clinical management. Early referral essentially requires three steps. The first step is therapeutic education, which includes information, sensitiveness, training and acceptance of the disease. The second step is the assembling of a multidisciplinary team in which the members are able to work together, coordinating and managing treatment protocols. These two steps allow the design of the third step, disease management, which consists of a methodology based on an integrated approach to the dis-ease allowing continuous improvement in medical care, in the patient's quality of life and a better use of economic resources.

[Census 2004 of the Italian Renal and Dialysis Units--Piemonte, Liguria and Valle d'Aosta]. / Censimento 2004 dei Centri di Nefrologia e Dialisi italiani. Piemonte--Liguria--Valle d'Aosta.

The Italian Society of Nephrology (SIN) promoted a national survey in order to obtain detailed information from all Renal and/or Dialysis Units using the on-line questionnaire (158 items) regarding structural and technological resources, medical workforce organisation and activity features. The purposes of this initiative were to obtain regional benchmarks as references for renal units and to describe the current Italian renal network in order to plan further interventions for the next 5 years. In this paper data of the first three Italian Regions (Piemonte, Liguria and Valle d'Aosta) which completed the survey (100% of the units) are reported. Main findings in the 3 Regions. A) Epidemiology: prevalence of dialysis patients = 709, 720, 787 pmp (per million population); prevalence of transplanted patients = 325, 387, 279 pmp; incidence of dialysis patients = 166, 191, 156 pmp; gross mortality of dialysis patients = 13.7, 15.0, 13.0%; distribution of vascular access in prevalent dialysis patients: arteriovenous fistula = 74, 83, 76%, central venous catheter = 18, 12, 15%, vascular graft = 8, 5, 9%. B) Structural resources: hospital's number of beds = 49, 72, 49 pmp, dialysis places = 166, 158, 164 pmp. C) Personnel resources: renal physicians = 44, 47, 41 pmp, renal nurses = 186, 194, 205 pmp; each renal physician takes care of 16, 15, 19 dialysis patients and each renal nurse cares for 3.8, 3.7, 3.8 dialysis patients. D) Activity: admission to hospital = 1507, 2392, 1606 pmp, renal biopsies = 109, 133, 57 pmp. Despite discrepancies in population density in the three Regions, most indexes are surprisingly similar and show the satisfactory level of renal care attained in the Northwestern Italian area. Further improvements in health care management can be predicted as a consequence of a direct comparison between needs and results in the various Regions of the Country.

Bone mass status in different degrees of chronic renal failure.

Bone mineral density (BMD) was evaluated in 69 patients with chronic renal failure (CRF) and in healthy controls matched for age, sex, and, for women, menopausal status. Both appendicular (predominantly cortical) and axial (predominantly trabecular) bone mass were measured. Appendicular BMD was measured by single photon absorptiometry on the distal forearm and axial BMD was measured by dual photon absorptiometry on the lumbar spine. Patients were divided into three groups on the basis of creatinine clearance: group 1, 58 to 36 ml/min; group 2, 30 to 18 ml/min; group 3, 15 to 9 ml/min. Both appendicular and axial BMD decreased with the worsening of renal failure. Parathyroid hormone levels were inversely correlated with the values of appendicular BMD. BMD values were significantly lower in postmenopausal than in premenopausal women. Months of menopause were inversely correlated with axial BMD values. Appendicular BMD was lower in CRF patients than in controls, and both appendicular and axial BMD were significantly lower in postmenopausal uremic women than in postmenopausal healthy women.

Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study.

This report notes the differences in the classification of the primary renal disease (PRD) used in different renal dialysis and transplant registries worldwide. The heterogeneity of coding systems complicates the comparative analysis of end-stage renal disease from different regions. Using data collected over two decades in the United States, Europe, and Australia/New Zealand, we present a method for reorganization of the classes of PRD that allows a straightforward comparison of retrospective data from these registries.

Effects of erythropoietin administration on blood pressure and urinary albumin excretion in rats.

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Kaposi's sarcoma in a patient with focal glomerulosclerosis.

We report the clinical features and outcome af a patient who presented Kaposi's sarcoma following immunosuppressive therapy for FGS; Cyclophosphamide and steroids were administered; the patient recovered after three months treatment with i.v. vinblastine.

Progress of renal osteodystrophy during continuous ambulatory peritoneal dialysis.

At present, only a few data are available on the effects of continuous ambulatory peritoneal dialysis (CAPD) on renal osteodystrophy. Twelve patients on CAPD were studied for one year, in order to evaluate the progress of renal osteodystrophy. Our results showed a downward trend of plasma calcium, a good control of phosphatemia, a significant increase of alkaline phosphatase and parathyroid hormone. We also found an important decrease of plasma vitamin D metabolites (25(OH)D3 and 1,25 (OH)2D3) and bone mineral content. Bone biopsy showed a general worsening of both secondary hyperparathyroidism and osteomalacia. Thus, we can conclude that CAPD alone is not able to control the evolution of renal osteodystrophy.

Recombinant human erythropoietin (rhEPO) treatment potentiates growth hormone (GH) response to growth hormone releasing hormone (GHRH) stimulation in hemodialysis patients.

On the basis of previously described effects of recombinant human erythropoietin (rhEPO) treatment on endocrine abnormalities present in uremia, we assessed the possible effect of treatment with rhEPO on growth hormone (GH) response to growth hormone releasing hormone (GHRH) in a group of uremic patients. Eight patients on maintenance hemodialysis for 12 to 228 months, not previously treated with rhEPO, were tested with 100 micrograms of GHRH i.v. in bolus before and after three months of rhEPO treatment (40 U/kg i.v. three times a week). Before treatment, the GH response to GHRH was characterized, in uremic patients, by remarkable differences in plasma GH values and in the pattern of response curve in single patients. The variability of GH response was not modified after rhEPO treatment; however, an overall potentiation of GH response with a significant increase of plasma GH (p = 0.017 at 15 min, p = 0.035 at 30 min after GHRH injection) was observed in the tests performed after treatment. rhEPO administration induced an evident improvement of anemia, blood hemoglobin concentration being 5.3-7.6 g/dl before and 9.1-11.3 g/dl after treatment; however a demonstrable correlation between the potentiation of GH response to GHRH and the increase of hemoglobin concentration was not observed.

Reduction of plasma levels of betathromboglobulin and platelet factor 4 during hemodialysis: a possible role for a short acting inhibitor of platelet aggregation.

Plasma levels of the platelet markers betathromboglobulin and platelet factor 4 are elevated in patients with chronic renal failure, and their levels in hemodialysis patients increase further during exposure to the dialysis membrane. The effectiveness of a short acting inhibitor of platelet aggregation in reducing the blood levels of betathromboglobulin and platelet factor 4 was assessed by means of a double blind cross over study. A statistically significant reduction of betathromboglobulin and platelet factor 4 levels was observed during treatment with the platelet inhibitor.

Biofiltration and calcium-phosphate metabolism.

We evaluated the effect of one session of biofiltration on calcium-phosphate metabolism in four uremic patients and compared the results with those of a previous traditional hemodialysis (Cuprophane membrane) session, on the same subjects. The most noteworthy results were: both total and ionized plasma calcium rose less in biofiltration; phosphate clearance and parathyroid hormone clearance were higher in biofiltration; plasma 25-OH D did not change in either dialysis technique.

Kinetics of anti-Xa activity during combined defibrotide-heparin administration in hemodialysis.

Defibrotide, a polydesoxyribonucleotide derivative with antithrombotic and fibrinolytic activity, capable of inducing the release of PGI2 from vascular endothelia, was proposed as an alternative to standard heparin coverage during blood dialysis for patients at risk of bleeding. The original procedure featured the preliminary washing of the dialysis circuit with heparin, which was then recirculated and eliminated, and the two drugs, heparin and defibrotide, are known to interact with each other. The purpose of this present study was to explore the ex-vivo heparin activity (assessed as anti-Xa activity) in diverse hemodialysis models using defibrotide (800 mg intravenous, in 4 bolus injections) and various dosages of heparin. Anti-Xa activity is negligible in dialysis conducted with defibrotide alone. When the circuit was prewashed with heparin (5000 and 2500 IU), there was evident anti-Xa activity (0.3-0.5 U/ml) in the first 30-60 minutes of dialysis; continuous heparin infusion (500 U/hour) resulted in high anti-Xa activity levels at the end of dialysis. Thus the best hemodialysis procedure for patients at high risk of bleeding should be one utilizing only defibrotide, or defibrotide plus small amounts of calcium heparin infused at the rate of 500 U/hour for not more than two hours.

Serum amylase and isoamylase in chronic renal failure.

In 37 patients with chronic renal failure (CRF) serum amylase was higher than in 33 normal subjects (483 U/L +/- SD 185 versus 267 +/- SD 66 U/L, p less than 0.05); while the percentage of pancreatic isoenzymes was within normal limits in 34 patients and only slightly increased in 3. Seventeen of the patients were on conservative treatment, 10 on hemodialysis and 10 on continuous ambulatory peritoneal dialysis; no significant differences in serum amylase levels were detected between these subgroups. No correlation was found between serum BUN or creatinine and serum amylase but a positive correlation was found between these enzyme levels and duration of CRF (p less than 0.05) in the patients on conservative treatment.

[Use of lactulose in the treatment of chronic renal failure]. / L'impiego del lattulosio nella terapia dell'insufficienza renale cronica.

The effectiveness and tolerance of lactulose were studied in 15 patients suffereing from terminal chronic renal insufficiency under conservative treatment with hypoproteic diet. The drug was administered in doses such that 2-4 soft faeces discharges were obtained daily and in most cases led to an increase in the feeling of wellbeing, a reduction in arterial pressure, a reduction in potassiaemia and frequently in azotaemia, with no change in residual renal function.

[Intravenous folinic acid and vitamin B12 supplementation and homocysteine concentration in hemodialysis patients]. / Supplementazione e.v. di acido folinico e vitamina B12 e concentrazioni di omocisteina nei pazienti emodializzati.

INTRODUCTION: Hyperhomocysteinemia is one of the causes of the increased incidence of cardiovascular disease in uremia. Since homocysteine (Hcy) metabolism depends on the availability of folate and vitamin B12, we have measured the effects of chronic i.v. supplementation of folinic acid and vitamin B12 in a group of patients on maintenance hemodialysis. METHODS: We compared the blood concentration of total Hcy (tHcy), vitamin B12 and folate and the intraerythrocyte concentration of folate in a group of 27 hemodialysis patients (Treated group), given an i.v supplementation with folinic acid (0.9 mg) and Vitamin B12 (cyanocobalamine 1.5 mg and hydroxycobalamine 1.5 mg) three times per week at the end of each dialysis session with those measured in a similar group of 28 hemodialysis patients without supplementation (No Treatment group). The patients were also characterized for the thermolabile variant (mutation C667-->T) of the enzyme methylene-tetrahydrofolate reductase (tMTHFR). RESULTS: High plasma levels (< 11.7 micromol/L) of tHcy were observed in 54/55 patients. T patients had Hcy values significantly lower than NT ones (31.7+/-3.6 vs. 1.1+/-8.3micromol/L, p < 0.05). Serum vitamin B12 (1200 73.6 vs. 762+/-72.2 pmol/L, p < 0.001) and intraerythrocyte folate levels were also significantly higher in the T group (2176+/-127 vs. 1511+/-156, p < 0.005), while no significant difference was observed for serum folate. The distribution of tMTHFR genotypes was similar in the two groups. Homozygous patients showed higher levels of Hcy in comparison with wild type patients both in the whole population (62.32+/-15.9 vs.30.43+/-3.2, p < 0.05) and in the NT group (87.8+/-25.3 vs.36.8+/-13.1., p < 0.05), while no significant difference was observed among genotypes in the T group. CONCLUSIONS: Uremic patients on hemodialysis, when supplemented with even low i.v. dose of folinic acid and vitamin B12, show significantly lower plasma levels of tHcy than non-supplemented patients.