Leonardo Cagnoli

The effect of on-line high-flux hemofiltration versus low-flux hemodialysis on mortality in chronic kidney failure: a small randomized controlled trial.

BACKGROUND Given the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD). STUDY DESIGN An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle. SETTING & PARTICIPANTS Prevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers. INTERVENTIONS Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32). OUTCOMES & MEASUREMENTS All-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method. RESULTS There was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06 versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54 mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 +/- 0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03). LIMITATIONS This is a small preliminary intervention study with a high dropout rate and problematic generalizability. CONCLUSION On-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index. A larger study is required to confirm these results.

Lymphocyte Subpopulations in Minimal-Change Nephropathy

It has been suggested that minimal-change nephropathy (MCN) may be related to a disorder of cell-mediated immunity. Lymphocyte cell-surface markers (E and EAC rosettes) and functional markers (mitogen

Electrophysiological response to dialysis: the role of dialysate potassium content and profiling.

UNLABELLED The task of dialysis therapy is, amongst other things, to remove excess potassium (K+) from the body. The need to achieve an adequate K+ removal with the risk of cardiac arrhythmias due to sudden intra-extracellular K+ gradient advises the distribution of the removal throughout the dialysis session instead of just in the first half. The aim of the study was to investigate the electrical behavior of two different K+ removal rates on myocardial cells (risk of arrhythmia and ECG alterations). Constant acetate-free biofiltration (AFB) and profiled K+ (decreasing during the treatment) AFB (AFBK) were used in a patient sample to understand, first of all, the effect on premature ventricular contraction (PVC) and on repolarization indices [QT dispersion (QTd) and principal component analysis (PCA)]. The study was divided into two phases: phase 1 was a pilot study to evaluate K+ kinetics and to test the effect on the electrophysiological response of the two procedures. The second phase was set up as an extended cross-over multicenter trial in patient subsets prone to arrhythmias during dialysis. Phase 1: PVC increased during both AFB and AFBK but less in the latter in the middle of dialysis (298 in AFB vs. 200 in AFBK). The PVC/h in a subset of arrhythmic patients was 404 +/- 145 in AFB and 309 +/- 116 in AFBK (p = 0.0028). QT interval (QTc) prolongation was less pronounced in AFBK than in AFB. Phase 2: The PVC again increased in both AFB and AFBK but less in the latter mid-way through dialysis (79 +/- 19 AFB vs. 53 +/- 13 AFBK). Moreover, in the most arrhythmic patients the benefit accruing from the smooth K+ removal rate was more pronounced (103 +/- 19 in AFB vs. 78 +/- 13 in AFBK). CONCLUSION It is not the K+ dialysis removal alone that can be destabilizing from an electrophysiological standpoint, but rather its removal dynamics. This is all the more evident in patients with arrhythmias who benefit from the K+ profiling during their dialysis treatment.

Assessment of Kidney Volume in Polycystic Kidney Disease Using Magnetic Resonance Imaging without Contrast Medium

Background/Aims: Total renal volume (TRV) is an important index to evaluate the progression of autosomal-dominant polycystic kidney disease (ADPKD). TRV has been assessed by manually tracing renal contours from CT or MR scans, often employing contrast medium (CM). We developed a fast and nearly automated technique based on the analysis of MR images acquired without CM injection for TRV quantification. Methods: 30 ADPKD patients underwent MRI. After the selection of one point inside each kidney for the entire volume, the automatic extraction of kidney contours was performed on each acquired slice; the segmentation procedure was based on region growing and on the application of morphological operators and curvature-based motion. The area inside each contour was calculated and TRV was derived. Volume measurements were validated by comparison with measurements obtained by stereology. Results: TRV estimated in patients was 768 ± 545 ml (range 161–3,111 ml). The automatic measurements were in excellent correlation with the manual ones (r = 0.99, y = x – 0.7), with a small bias and narrow limits of agreement in both absolute (–5 ± 37 ml) and percentage (–0.6 ± 9.6%) terms. Conclusion: This preliminary study showed the feasibility of a fast and nearly automated method for determining TRV; importantly it does not require the use of potentially nephrotoxic CM.

Cardiac response to hemodialysis with different cardiovascular tolerance: Heart rate variability and QT interval analysis

A therapy‐specific worsening of cardiovascular stability during bicarbonate dialysis (BD) with respect to acetate‐free biofiltration (AFB) have been previously reported. We further investigated the impact of the 2 therapies on electrocardiographic parameters in order to gain novel insight into the cardiac responses. Holter ECG acquired during hypotension‐free sessions (12 BD+12 AFB) were retrospectively analyzed. R–R intervals were extracted from ECG recordings. An autoregressive spectral technique was used to compute low‐ and high‐frequency (LF and HF) components of heart rate variability (HRV). QT interval duration was measured with a computer‐assisted technique and corrected for HR. In BD the LF component of HRV after an initial increase was slowly depressed with respect to AFB (p<0.05). QT duration showed a significant (p<0.01) hemodialysis‐induced reduction. QT shortening was more pronounced (p<0.05) in BD than in AFB (−31 vs. −10 ms), even after correction for HR (p<0.05). Cardiac electrical activity is significantly affected by the hemodialysis technique. The decrease in the LF component of HRV and the QT shortening are coherent with the worse cardiovascular tolerance observed in BD and with the hypothesis of an enhanced production of endogenous nitric oxide.

Prognostic value of T lymphocyte subset ratio in idiopathic membranous nephropathy

The behavior of T lymphocyte subsets was studied in 39 Italian patients with nephrotic syndrome due to idiopathic membranous nephropathy. They took part in a long-term prospective and randomized therapeutic trial based on the 6-month administration of methylprednisolone and chlorambucil. The lymphocyte subsets were evaluated by monoclonal antibodies at the beginning of the trial and at the end of the follow-up period in 23 treated and in 16 untreated patients. Our data seem to suggest that a higher helper-inducer/suppressor-cytotoxic cell ratio before therapy may be a good prognostic index of improved proteinuria. Moreover, the therapeutic schedule does not seem to induce a long-lasting abnormality in cellular immunity.

Cell interposition in glomerular capillary walls in cryoglobulinemic glomerulonephritis (CRYGN). Ultrastructural investigation of 23 cases.

The present report describes ultrastructural findings on twenty-three cases of CRYGN showing membranoproliferative pattern under light microscopy. Attention was paid to the presence of double contoured peripheral basement membranes and to the characteristics of the interposed cells. The latter, according to the well known characteristics of membranoproliferative GN, are thought to be mesangial in nature. In fact, mesangial cells were found in 8 cases only, always associated with monocytes. Only monocytes were recorded in 12 cases, whereas in other 3 cases double contours were not connected to cell interposition. Despite similarities under light microscopy, CRYGN is therefore rather different from idiopathic membranoproliferative GN because of the prevalence of exudative changes, mainly due to monocyte infiltration, over proliferative lesions.

Calcium profiling in hemodiafiltration: a new way to reduce the calcium overload risk without compromising cardiovascular stability.

Background Low and high dialysate calcium (Ca2+) content may have positive and harmful effects depending on the considered pathological aspect: hemodynamic instability, cardiac arrhythmias, parathormone release, adynamic bone disease, cardio-vascular calcifications. We hypothesized that a time-profiled Ca2+ concentration would keep the cardiovascular advantages of high Ca2+ but would reduce the risk of calcium overload. Methods A prospective, multicenter study using a particular hemodiafiltration technique that allows the profiling of electrolytes was designed. Patients (n = 22) underwent randomly a 3-week dialysis session with low and high constant dialysate Ca2+ (LdCa, 1.25 mM and HdCa, 2 mM) and profiled Ca2+ (PdCa), respectively. Plasma and spent dialysate Ca2+, systolic and diastolic arterial pressure (SAP, DAP) and QT interval corrected for heart rate (QTc) were analyzed. Results Plasma Ca2+ concentration decreased in LdCa, whereas it increased in HdCa and to a lesser extent, in PdCa. Total amount of Ca2+ given to the patient in PdCa (15.5 ± 1.0 mmol) was higher than in LdCa (4.3 ± 1.6 mmol) but lower than in HdCa (21.9 ± 3.3 mmol). SAP and DAP decreased in LdCa, whereas it was almost constant in both HdCa and PdCa. QTc significantly increased, up to critical values (>460 msec), only during LdCa. Conclusions PdCa seems to retain the advantages of high Ca2+ in terms of hemodynamic stability and modification of QTc while reducing the excessive positive calcium balance typical of dialysis with high Ca2+ content.

Lymphocyte hyporesponsiveness during edema, proteinuria and hypertension (EPH) gestosis

SummaryIn vitro immunological tests showed that patients with pre-eclampsia are characterized by a greater degree of lymphocyte hyporesponsiveness to mitogens during pregnancy than normotensive controls. Thus, a relationship has been hypothesized between the hypoimmune lymphocyte response and the pathogenesis of the disease. We studied 20 non-pregnant healthy volunteers (group a), 11 women with a normal pregnancy (group b) and 13 women with EPH gestosis (group c). In all patients we determined the number of lymphocytes and the lymphocyte function (PHA, Con A, PWM responsiveness) in autologous and homologous plasma during pregnancy and 5 to 30 days after delivery. The mean values of the number of EAC and E rosettes in the three groups studied were similar. The mean values of the mitogenic response to PHA in autologous plasma were significantly reduced in both groups b and c in comparison with group a, but there was no statistical difference between groups b and c. The PHA lymphocyte responsiveness returned to normal in both homologous and autologous plasma after delivery. Our data demonstrate that no difference exists between pregnant women with and without pre-eclampsia as regards impaired cell-mediated lymphocyte responsein vitro. Moreover, the diminished lymphocyte responsiveness to mitogens during pregnancy seems to be due to humoral circulating factor(s).

Membranoproliferative Glomerulonephritis: Correlations between Immunological and Histological Findings

34 adult patients with membranoproliferative glomerulonephritis are reviewed; the diagnosis was based on histological studies, by light and electron microscopy. Hypocomplementemia was detected in 67.6