Echocardiography and right ventricular function in NKF stage III cronic kidney disease: Ultrasound nephrologists' role.

TAPSE measurement during echocardiography is a well known measure of right heart systo-diastolic function. Low TAPSE means reduced cranio-caudal excursion of tricuspidal annulus, sign of both reduced ejection fraction and reduced distensibility of right ventricle. It is a good prognostic index for cardiac mortality risk in CHF patients, adding significant prognostic information to NYHA stadiation. Nephrologists do not always fully aware of right ventricular function in their patients affected by chronic renal failure (CRF), even if this datum is probably crucial in vascular access policy. Our study was designed to study right ventricle function and TAPSE on 202 patients affected by moderate chronic renal failure, free from overt pulmonary hypertension. TAPSE, PAPs, right chambers diameters, classical Framingham factors, estimated glomerular filtration rate were recorded. TAPSE was reduced (<23 mm) in 43% of patients enrolled, while dilated right chambers were present in 24%. PAPs exceeded 30 mmHg in 29% of patients. Echocardiographic signs of left ventricular hypertrophy were found in 36% of patients. The ejection fraction was normal in all patients. Statistical analysis showed a significant indirect correlation between TAPSE and PAPs and between TAPSE and tele-diastolic diameters and volumes of the right ventricle, while a direct correlation was observed between TAPSE and Framingham score. TAPSE showed a bimodal distribution, with a subpopulation "low TAPSE - high PAPs", next to a population characterized by normal values ??for both parameters. A reduction in compliance and systolic function of the right heart chambers is quite early and frequent in course of CKD, a fact that the nephrologist should take in due consideration, managing blood volume or planning vascular access for hemodialysis.

Predictive role of duplex Doppler ultrasonography in the diagnosis of acute renal obstruction in patients with unilateral renal colic.

OBJECTIVE: The aim of our study was to assess the role of Doppler ultrasonography (DU) by resistive index (RI) and the difference of the RI (DeltaRI) in patients with acute unilateral renal obstruction. PATIENTS AND METHODS: We studied 36 consecutive patients (12 female, 24 male; mean age 45.6 +/- 8.4 years) with suspected renal colic by intravenous pyelography (IVP) and DU with determination of the RI and the Delta RI. A RI of >= 0.70 and a DeltaRI of >= 0.06 were considered suggestive of obstruction. IVP was considered as the "gold standard". RESULTS: In the studied population, RI was 0.664 +/- 0.060 in the affected kidney site of symptoms and 0.614 +/- 0.025 in the contralateral one, with an overall Delta RI of 0.049 +/- 0.062. At IVP, 14 patients resulted within normal range (Group A; 39%), 6 patients showed lithiasis without obstruction (Group B; 17%), 8 patients showed delayed excretion of the contrast medium (Group C; 22%), and 8 patients showed a functional exclusion of the kidney (Group D; 22%). One-way analysis of variance showed the IVP group significantly related to Delta RI with the highest values in Groups C (DeltaRI of 0.093 +/- 0.051; p<0.001) and D (DeltaRI of 0.116 +/-0.030; p<0.001) in comparison with Group A (DeltaRI of 0.001 +/-0.038) and Group B (DeltaRI of 0.015 +/-0.024). No differences were detected between Groups C and D (p=0.223) and between Groups A and B (p-0.472). DeltaRI measurement with DU permitted to predict the renal obstruction with a sensitivity of 93.8%, a specificity of 95.0% and an accuracy of 94.4%. CONCLUSIONS: Intrarenal Doppler ultrasonography represents a sensitive and highly specific test that can significantly contribute to the diagnosis of obstruction in patients with acute renal colic. It should be used as the first line imaging method in suspected acute renal colic, as well as for patients with renal insufficiency, pregnant women or for patients with adverse reactions to contrast media

Doppler ultrasound and renal artery stenosis: An overview.

Renovascular disease is a complex disorder, most commonly caused by fibromuscular dysplasia and atherosclerotic diseases. It can be found in one of three forms: asymptomatic renal artery stenosis (RAS), renovascular hypertension, and ischemic nephropathy. Particularly, the atherosclerotic form is a progressive disease that may lead to gradual and silent loss of renal function. Thus, early diagnosis of RAS is an important clinical objective since interventional therapy may improve or cure hypertension and preserve renal function. Screening for RAS is indicated in suspected renovascular hypertension or ischemic nephropathy, in order to identify patients in whom an endoluminal or surgical revascularization is advisable. Screening tests for RAS have improved considerably over the last decade. While captopril renography was widely used in the past, Doppler ultrasound (US) of the renal arteries (RAs), angio-CT, or magnetic resonance angiography (MRA) have replaced other modalities and they are now considered the screening tests of choice. An arteriogram is rarely needed for diagnostic purposes only. Color-Doppler US (CDUS) is a noninvasive, repeatable, relatively inexpensive diagnostic procedure which can accurately screen for renovascular diseases if performed by an expert. Moreover, the evaluation of the resistive index (RI) at Doppler US may be very useful in RAS affected patients for predicting the response to revascularization. However, when a discrepancy exists between clinical data and the results of Doppler US, additional tests are mandatory.

Color Doppler ultrasonography percutaneous transluminal angioplasty of vascular access grafts.

Percutaneous transluminal angioplasty (PTA) is a possible treatment for stenosis. This study aimed to verify the impact of a vascular access (VA) surveillance protocol, based on the detection of functional changes and their correction by a new PTA method for VA performed under color Doppler ultrasonography (CDU) guidance. We divided the patients into two groups: group A, before May 1999 (retrospective study) without the surveillance protocol, and group B, from 1 May 1999 to January 2001 (prospective study) with the surveillance protocol. Access blood flow (Qa) was assessed every 4 weeks by ultrasound velocity dilution. In cases of a reduction of >or=35% from the baseline value, VA was examined using CDU: if a stenosis >50% was detected, angioplasty was performed. In cases of Qa reduction <35% we continued monitoring. By Coxs multivariate analyses, only the use of PTA with or without stenting reduced the relative risk of thrombosis by 64% during the follow-up (p=0.017 confidence intervals 88%-15%) in group B patients. Secondary patency was 80% for VA in which we performed PTA with or without stenting at 18 months, and 58% at 18 months in which we did not perform PTA. Our data show how PTA under CDU is useful to maintain and to improve graft patency. This PTA under CDU guidance allows patients to avoid surgical intervention, hospitalization, and adverse reactions to contrast media and exposure to ionizing radiation, with reduced cost and with better graft survival.

[P value and confidence intervals: reporting and interpreting the result of a clinical study]. / Guida al corretto uso della P e degli Intervalli di Confidenza nella lettura e presentazione dei risultati di uno studio clinico.

The main purpose of statistics in the analysis of clinical and epidemiological studies is to summarize data and information, as well as assess variability, trying to distinguish between chance findings and results that may be replicated upon repetition. Statistical analyses only convey the effect of chance element in data (random error). Statistics cannot control non-sampling errors concerning study design, conduct and methods adopted. At the end of the study, a result is defined statistically significant if the observed difference in the outcome variable is too large to be attributed to chance. A small P value provides evidence against the null hypothesis (of no effect), since data have been observed that would be unlikely if the null hypothesis was true. However, confidence intervals estimate separate the two data dimensions (strength of the relation between exposure and disease, and precision with which the relation is measured), and add to the hypothesis testing useful information for finding interpretation and further research.

[Clinical relevance of study results]. / Rilevanza dei risultati di uno studio clinico.

The critical appraisal process of available evidence includes the evaluation of clinical importance of the study findings. This should coincide with the minimum worthwhile effect expected by the investigators in the study design and planning. In hard outcome studies it can be quantified by the absolute risk difference between groups and its reciprocal, known as number needed to treat to avoid one adverse event, or benefit (NNTB). The number needed to treat to produce harmful consequences of treatment (NNTH) should also be taken into account. Finally these effect measures, like risks and incidence proportions, are usually rough estimates of the true effects, due to non-complete follow-up of the observations under study. Underlying assumptions and design issues are especially important to assess the clinical relevance of any results.

Reduction in urea distribution volume over time in clinically stable dialysis patients.

We have previously shown that, assuming urea distribution volume (V) remains constant for 1 month, ionic dialysance (ID) allows the dialysis dose to be calculated without the need for blood sampling. The aim of this multicenter study was to verify whether the assumption of a constant V can be extended to 1 year. In clinically stable patients receiving thrice-weekly hemodialysis at 13 dialysis centers, V and Kt/V were assessed during three dialysis sessions at baseline and 1 year later using ID as dialyzer urea clearance and the single-pool urea kinetic model. Baseline albumin, hemoglobin, and C reactive protein were prespecified covariates for predicting the change in V over time. Of the 52 enrolled patients, 40 (25 males; age 63.0+/-13.5 years) completed the study. Baseline end-dialysis body weight (62.4+/-13.7 kg) showed a non-significant 1% reduction during follow-up (-0.6+/-2.8 kg; P=0.175), whereas V significantly decreased from 29.0+/-6.8 to 27.4+/-6.0 l (-1.6+/-3.0 l or 4.5%; P=0.002). The reduction in V was greater when baseline albumin was lower (P=0.001) and baseline V was higher (P=0.005). The single-pool K(t)/V calculated using baseline V underestimated the actual value by 0.07+/-0.16 (P=0.008). The slight underestimate of Kt/V during follow-up suggests that annual V evaluations may be sufficient for dialysis dose quantification as the only risk is underestimating the actually delivered dialysis dose. However, the relationship between baseline albumin and the reduction in V over time may have nutritional value, and suggests more frequent V evaluations.

Peritoneal transport assessment by peritoneal equilibration test with 3.86% glucose: a long-term prospective evaluation.

The peritoneal equilibration test (PET) with 3.86% glucose concentration (3.86%-PET) has been suggested to be more useful than the standard 2.27%-PET in peritoneal dialysis (PD), but no longitudinal data for 3.86%-PET are currently available. A total of 242 3.86%-PETs were performed in 95 incident PD patients, who underwent the first test during the first year of treatment and then once a year. The classical parameters of peritoneal transport, such as peritoneal ultrafiltration (UF), D/D(0), and D/P(Creat), were analyzed. In addition, the absolute dip of dialysate sodium concentration (DeltaD(Na)), as an expression of sodium sieving, was studied. D/D(0) was stable, and a progressive decrease in UF was observed after the second PET, whereas D/P(Creat) firstly increased and then stabilized. DeltaD(Na) was the only parameter showing a progressive decrease over time. On univariate analysis, D/D(0) and DeltaD(Na) were found to be significantly associated with the risk of developing UF failure (risk ratio (RR) 0.987 (0.973-0.999), P=0.04, and RR 0.768 (0.624-0.933), P=0.007, respectively), but on multivariate analysis only DeltaD(Na) showed an independent association with the risk of developing UF failure (RR 0.797 (0.649-0.965), P=0.020). UF, D/D(0), and D/P(Creat) changed only in those patients developing UF failure, reflecting increased membrane permeability, whereas DeltaD(Na) significantly decreased in all patients. The 3.86%-PET allows a more complete study of peritoneal membrane transport than the standard 2.27%-PET. DeltaD(Na) shows a constant and significant reduction over time and is the only factor independently predicting the risk of developing UF failure in PD patients.

[Water quality cuts down the chronic inflammatory risk: how to obtain it and keep it over time]. / La qualità dell'acqua abbatte il rischio infiammatorio cronico: come produrla e garantirla nel tempo.

BACKGROUND: Every week, approximately 400 liters of water used for dialysate production come into direct contact, through the semi-permeable membrane of the dialyzer, with the dialysis patient's blood stream. Therefore, submitting municipal water to an adequate depuration process before its use for dialysis becomes necessary. METHODS: Problems related to the implementation, updating and management of a dialysis water treatment system are analyzed. The results of the most recent multicenter studies on dialysis fluids quality are also reviewed. RESULTS: The best approach to plan, implement and manage a dialysis water treatment system, first, consists of defining the standards of chemical and microbiological water quality. The most diffused and commonly accepted standards are those recommended by the Association for Advancement of Medical Instrumentation (AAMI) and the European Pharmacopea (EP), which allow a maximum bacterial growth of, respectively, 200 CFU/ml and 100 CFU/mL and a maximum endotoxin concentration of 2 IU/mL and 0.25 IU/mL. A modern dialysis water treatment system provides a final purification process, mainly by reverse osmosis (RO), together with different pre-treatment levels and a hydraulic distribution circuit. Therefore, as RO produces water of optimal chemical and microbial quality, all efforts in the dialysis unit must be aimed at keeping this quality as constant as possible over time, by carrying out effective maintenance strategies and system disinfection. Nevertheless, several multicenter studies reported that 7-35% of water samples exceed a bacterial growth of 200 CFU/mL and that 44% of them display endotoxin concentrations >5 IU/mL. CONCLUSIONS: The results of multicenter studies indicate that the microbial quality of dialysis fluids is, unfortunately, still an often neglected problem. Evidence of a possible relationship between dialysis fluid contamination and patient morbidity, as well as the availability of systems and machines allowing purity levels that were unimaginable only a few years ago, must be a stimulus for modifying clinical practices and starting the improvement processes aimed at maximally reducing the risk of microbial contamination in the dialysis water, as already done with chemical contamination.

Long-term immunotherapy with low-dose interleukin-2 and interferon-alpha in the treatment of patients with advanced renal cell carcinoma.

BACKGROUND: The objective of this study was to evaluate response, toxicity, and immunologic effects of an original immunotherapy schedule based on repeated cycles of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFNalpha) in patients with metastatic renal cell carcinoma (mRCC). METHODS: Fifty patients who underwent nephrectomy received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFNalpha twice weekly for 4 consecutive weeks. The cycle was regularly repeated indefinitely at 4-month intervals in all patients, irrespective of their response. rIL-2 (1 x 10(6) IU/m(2)) was administered every 12 hours on Days 1 and 2 and once per day on Days 3-5 of each week; rIFNalpha (1.8 x 10(6) IU/m(2)) was given on Days 3 and 5. Toxicity was graded according to the World Health Organization (WHO) criteria. Forty percent of the patients had only one metastatic disease site at the time of treatment. The Kaplan-Meier method was used to estimate survival, and an analysis of variance was used to evaluate the effects on leukocytes and lymphocyte subsets over time. RESULTS: A total of 241 cycles were administered. One patient achieved a complete response, and five patients achieved a partial response. Five patients had stable disease, and 30 patients had progressive disease. Nine patients were not evaluable for response. The overall response rate was 12% (95% confidence interval, 3-21%) on the basis of an intent-to-treat analysis. The 36-month survival probability for all 50 patients was 47%. Treatment-related toxicity was limited to WHO Grades 1 and 2. Both lymphocyte and eosinophil levels significantly increased after all cycles (by 42% and 353%, respectively). The treatment also induced significant increases in the CD25 positive (24%), CD56 positive (28%), and CD3 negative/CD56 positive (54%) lymphocyte subsets. CONCLUSIONS: Long-term, repeated treatment with low doses of rIL-2 and rIFNalpha is feasible in patients with mRCC. The schedule induces clinical response rates and survival probabilities are similar to those obtained using higher doses.

Dialysis: its role in optimizing recombinant erythropoietin treatment.

Although iron deficiency is probably the most important factor affecting response to recombinant erythropoietin (Epo, epoetin), other factors are of significance, including dialysis adequacy. Additionally, water treatment and distribution, sterilizants and the quality of the dialysate in terms of trace elements (particularly chloramine) are of importance in relation to erythropoiesis inhibition. Microbiological or pyrogenic contamination can cause or aggravate anaemia in haemodialysis patients, and the impact of enhanced production of cytokines should be taken into consideration. By removing small and (possibly) medium/large molecules, adequate dialysis is of paramount importance in correcting anaemia and optimizing epoetin therapy. The biocompatibility of dialysis membranes and flux are other important factors. As yet unknown uraemic toxins may suppress erythropoiesis and contribute towards the development of anaemia. It is reasonable to hypothesize that, because anaemia improves after the start of dialysis with cellulose membranes, low molecular weight erythropoiesis inhibitors are involved, as well as medium/large molecular weight inhibitors, which are removed by more permeable membranes. However, in highly selected, adequately dialysed patients without iron or vitamin depletion, the effects of dialysis membrane type on haematological parameters and epoetin efficacy are smaller than might be expected from the results of uncontrolled studies. Improvement in anaemia has been observed using on-line haemofiltration, haemodiafiltration, and sterile dialysate. The results of prospective, randomized trials examining the impact of these factors on anaemia and the effectiveness of epoetin treatment are eagerly awaited.

Role of proteinuria reduction in the progression of IgA nephropathy.

UNLABELLED: Proteinuria has been shown to play a causal role in the progression towards ESRD of IgA nephropathy (IgAN). We demonstrated that steroids are effective in reducing proteinuria and preserving renal function. AIM: to evaluate the long-term effect of steroids in IgAN patients (6th year evaluation) and better clarify the role of proteinuria reduction in slowing down the progression. METHODS: multicenter randomized controlled trial of 86 adult IgAN patients with serum creatinine < or = 1.5 mg/ dL and moderate proteinuria. They received either supportive therapy or methylprednisolone 1-g i.v. for three days at months 1, 3, and 5, plus oral prednisone (0.5 mg/kg every other day for six months). RESULTS: Proteinuria significantly decreased in the treated patients (from 2.0+/-0.60 g/24 h at baseline to 1.0+/-0.68 g/24 h at six months) and remained stable till the 6th year (0.67+/-0.5 g/24 h), it slightly decreased in the control group. Six-year renal survival was significantly better in the steroid than in the control group: 9 patient (20.9%) in the steroid group and 15 (34.8%) in the control group reached the primary end-point of a 50% increase in serum creatinine from baseline. Five controls and none of the steroid-treated patients started dialysis. Steroid-treated patients did not experience any major side effects during follow-up. CONCLUSIONS: Steroids significantly reduce proteinuria and protect against renal function deterioration in IgAN patients. Early reduction of proteinuria could also be marker of a persistent reduction in its levels over time and of a better outcome in the long term.

Effect of sodium pool changes on blood pressure in patients undergoing PFD: design of a prospective randomized multicenter trial.

Blood pressure control is important during dialysis and the interdialytic period because of the frequency and potential seriousness of hypotension and hypertension. Water and sodium removal play an important role in the genesis of intradialytic cardiovascular instability or hypertension. Changing dialysate sodium concentrations without the aid of a kinetic model can sometimes give good results but is only an empirical approach. Therefore, this clinical trial was designed to prospectively investigate the advantages of changes in the sodium pool on the blood pressure profile of patients undergoing paired filtration dialysis (PFD). The hypothesis to be tested is whether using a dialysate conductivity which, according to the conductivity kinetic model, ensures that the conductivity of the ultrafiltrate at the end of each dialysis session is 0.3 mS/cm more (B) or less (C) than the mean during the run-in period, improves blood pressure control either in patients prone to intradialytic hypotension or patients who are hypertensive or normotensive with antihypertensive treatment. Patients will be randomly allocated to one of two treatment sequences (where treatment A is standard PFD): AABB or ABAA for patients with intradialytic hypotension; AACC or ACAA for hypertensive patients. During the experimental phase arterial blood pressure will be measured and symptoms reported by the patients will be recorded.

Long-term treatment with low doses of interleukin-2 and interferon-alpha: immunological effects in advanced renal cell cancer.

PURPOSE: We aimed to determine the immunological effects of low doses of recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) in patients bearing advanced renal cell carcinoma. METHODS: Twenty-seven patients received therapeutic cycles consisting of subcutaneous rIL-2 for 5 days per week and intramuscular rIFN-alpha twice weekly, for 4 consecutive weeks. The cycle was repeated indefinitely at regular 4-month intervals, for all patients. rIL-2 (1 x 10(6) IU/m2) was administered every 12 h on days 1 and 2 and once a day on days 3-5 of each week; rIFN-alpha (1.8 x 10(6) IU/m2) was given on days 3 and 5. In the enrolled patients, total and differential white blood cell counts, phenotypic analysis of some lymphocyte subsets, and soluble IL-2 receptor (sIL-2R), were investigated before and after each of the first six cycles of therapy (about 24 months of follow-up). RESULTS: The cycles of immunotherapy induced a significant increase of total lymphocytes (37%, P < 0.001), eosinophils (222%, P < 0.001), CD25+ cells (27%, P=0.004), sIL-2R (174%, P < 0.001) and natural killer (NK) cells (CD3-CD56+) (61%, P < 0.001); the subset that expresses CD56 with high density (CD56+ bright) expanded more (233%, P < 0.001) than the subset expressing the same marker with low density (CD56+ dimmer) (15%, P = 0.043). Unlike the previous subsets, the treatment decreased significantly T-lymphocytes with NK cell marker (CD3+ CD56+) (28%, P = 0.011). No significant differences of effectiveness were found among the subsequent treatment cycles, except for CD25+ cells and sIL-2R (P = 0.036 and P = 0.005, respectively): the increase induced by immunotherapy was maximum after the first cycle and decreased progressively thereafter. CONCLUSIONS: Long-term repeated cycles of low-dose immunotherapy induced repeated and significant expansion of one of the most important lymphocyte subsets for the non-MHC-restricted immune response to the tumour mass: CD3-CD56+ cells.