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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).An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle.Prevalent patients with ESRD (age, 16 to 80 years; vintage6 months) receiving renal replacement therapy at 20 Italian dialysis centers.Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32).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.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; P0.05). 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 (P0.001). 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).This is a small preliminary intervention study with a high dropout rate and problematic generalizability.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.

Background. Automatic systems for stabilizing blood pressure (BP) during dialysis are few and only control those variables indirectly related to BP. Due to complex BP regulation under dynamic dialysis conditions, BP itself appears to be the most consistent input parameter for a device addressed to preventing dialysis hypotension (DH). Methods. An automatic system (ABPS, automatic blood pressure stabilization) for BP control by fluid removal feedback regulation is implemented on a dialysis machine (Dialog Advanced, Braun). A fuzzy logic (FL) control runs in the system, using instantaneous BP as the input variable governing the ultrafiltration rate (UFR) according to the BP trend. The system is user-friendly and just requires the input of two data: critical BP (individually defined as the possible level of DH risk) and the highest UFR applicable (percentage of the mean UFR). We evaluated this system’s capacity to prevent DH in 55 RDT hypotension-prone patients. Sessions with (treatment A) and without (treatment B) ABPS were alternated one-by-one for 30 dialysis sessions per patient (674 with ABPS vs 698 without). Results. Despite comparable treatment times and UF volumes, severe DH appeared in 8.3% of sessions in treatment A vs 13.8% in treatment B (� 39%, P ¼ 0.01). Mild DH fell non-significantly (� 12.3%). There was a similar percentage of sessions in which the planned body weight loss was not achieved and dialysis time was prolonged. Conclusions. In conclusion, FL may be suited to interpreting and controlling the trend of a determined multi-variable parameter like BP. The medical knowledge of the patient and the consequent updating of input parameters depending on the patient’s clinical conditions seem to be the main factors for obtaining optimal results.

Fabry disease (FD) is a rare X-linked disorder characterized by low or absent activity of the lysosomal enzyme α-glycosidase-A that leads to progressive accumulation of glycosphingolipids in different organs and tissues. Clinical manifestations vary from classic to atypical forms characterized by one prevalent organ involvement, and a renal variant has been described in men but not in women. However, little is known about renal manifestation in females affected by FD. We herein report a case of a 22-year-old female with isolated and persistent microalbuminuria as the only sign of FD. In light of the importance of early recognition and treatment of FD organ damage, this case should call for future studies to determine how to assess organ damage, investigate the existence of a 'renal variant' in FD female patients and determine when best to start enzyme replacement therapy (ERT).

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.

BACKGROUND The aim of this multicentre collaborative study was to compare the progression of renal disease in children and adults with Henoch-Schonlein purpura (HPS) nephritis selected on the basis of IgA-dominant renal deposits and biopsy material available for review. METHODS The analysis was performed in 152 patients (95 adults and 57 children or = 1 year up to 20 years (4.9 +/- 3.4 years in adults and 4.8 +/- 3.9 years in children). RESULTS Renal histology and clinical presentation were similar in both age groups: crescents were found in 36% of adults and 34.6% of children (in only 2.7% of adults and 1.9% of children involving > 50% of glomeruli), nephrotic-range proteinuria in 29.5% of adults and 28.1% of children and functional impairment in 24.1% of adults and 36.9% of children. The outcome was similar for both age groups (remission, 32.5% of adults and 31.6% of children; renal function impairment, 31.6% of adults and 24.5% of children). Endstage renal disease was observed in 15.8% of adults and in 7% of children. Renal function survival at 5 years was not significantly different in the two groups (85% in adults and 95% in children) and at 10 years it was approximately 75% in both groups. None of the children died and adult survival was 97% at 5 years. In adults at presentation, renal function impairment (P < 0.02) as well as proteinuria higher than 1.5 g/day (P < 0.02) and hypertension (P < 0.001) were negative prognostic factors. Multivariate analysis stressed the main statistical relevance of proteinuria (relative risk 2.37, P < 0.02). Conversely, in children no definite level of proteinuria, hypertension or other data were found to be associated with poor prognosis. CONCLUSIONS Among patients with a clinical presentation which warrants renal biopsy, HSP nephritis has a similar prognosis in children and adults. The evolution is more predictable in adults than in children.

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.

Background In Fabry disease, end-stage renal disease (ESRD) and severe neurologic and cardiac complications represent the leading causes of late morbidity and mortality. A comprehensive Italian nationwide survey study was conducted to explore changes in cardiac status and renal allograft function in Fabry patients on renal replacement therapy (RRT) and enzyme replacement therapy (ERT). Methods This study was designed as a cross-sectional survey study with prospective follow-up. Of the 34 patients identified via searches in registries, 31 males and 2 females who received RRT and ERT (agalsidase beta in 30 patients, agalsidase alpha in 3) were included. Left ventricular mass index (LVMI), interventricular septal thickness at end diastole (IVSD), left ventricular posterior wall thickness (LVPWT) and renal allograft function were assessed at ERT baseline and subsequently at yearly intervals. Results The patients in the dialysis and transplant groups had been started on dialysis at age 42.0 and 37.1 years (mean), respectively, and patients in the transplant group received their renal allograft at age 39.8 years (mean). The mean age at the start of ERT was similar, 44.1 and 44.6 years, respectively. The mean RRT follow-up was 61.1 and 110.6 months for dialysis and transplant patients, respectively, whereas the ERT duration was 45.1 and 48.4 months, respectively. Cardiac parameters increased in dialysis patients. In transplant patients, mean LVMI seemed to plateau during agalsidase therapy at a lower level as compared to baseline. Decline in renal allograft function was relatively mild (-1.92 ml/min/year). Agalsidase therapy was well tolerated. Serious ERT-unrelated events occurred more often in the dialysis group. Conclusions Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.

BACKGROUND: Although sudden death is one of the most frequent causes of death in haemodialysis (HD) patients, the problem of cardiac arrhythmias, the major cause of these outcomes, has been little discussed. METHODS: In 30 arrhythmia-prone HD patients, we compared the arrhythmogenic effects of two dialysis techniques differing in dialysate potassium (K) content. Each patient underwent Acetate-Free Biofiltration sessions with constant (2.5 mEq/l) K (AFB) and sessions with decreasing intra-HD K (AFBK), according to a crossover single blind design. Holter ECG recording and plasma electrolyte measurements were performed during each dialysis session. RESULTS: There was a tendency in the whole sample for arrhythmia appearance in AFBK to be reduced as compared to AFB throughout the 24 hr period, although this reduction was not statistically significant. In the subset of patients sensitive to dialysis as far as arrhythmia onset is concerned, AFBK was systematically less arrhythmogenic than AFB (P < 0.01). The highest difference was achieved around the 14th hour after the end of dialysis, when the premature ventricular contractions in AFB were 3.9 times higher than in AFBK (P < 0.05). Potassium kinetics differed between the two procedures. At the first hour of treatment, the plasma K concentration was lower in AFB than in AFBK (3.67 +/- 0.15 mEq/l in AFB vs 4.06 +/- 0.13 mEq/l in AFBK, P = 0.05). CONCLUSIONS: Our study shows a greater arrhythmogenic activity with the use of a constant and relatively low K concentration as compared to decreasing K profiling in dialysis-sensitive arrhythmic patients. Smoother K removal may well engender a kind of protective effect.

We report a case of membranous lupus nephritis with a previous history of long-standing nephrotic syndrome which developed an acute renal failure due to bilateral renal-vein thrombosis superimposed on a calcified thrombus of the inferior vena cava eight years after the diagnosis. The occurrence of acute renal-vein thrombosis is a possible but rarely described complication of systemic lupus erythematosus. The presence of a calcified thrombus of the inferior vena cava has been described in only one adult patient until now. An aggressive thrombolytic therapy with urokinase permitted the fresh thrombus to be dissolved with a marked improvement in renal function.

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.

Factors predictive of renal outcome were investigated in 219 cases of biopsy-proven Henoch-Schönlein purpura nephritis (HSPN); 83 children and 136 adults enrolled in a national study were followed up for up to 27 years (median, 4.5 years).The criterion for defining disease progression was time elapsed until doubling of baseline creatinine level and until dialysis therapy. Age, sex, data at onset (renal function, proteinuria, hematuria, hypertension, and crescents), and data during follow-up (proteinuria and therapy) were tested as covariates.Multivariate Cox regression analysis indicated the following parameters as independent prognostic predictors: age (adults versus children, relative risk, 3.57; 95% confidence interval, 1.18 to 10.79; P = 0.024 for creatinine level doubling; relative risk, 14.89; 95% confidence interval, 1.72 to 129.07; P = 0.014 for dialysis therapy), sex (females versus males, relative risk, 5.71; 95% confidence interval, 1.67 to 19.55; P = 0.006 for creatinine level doubling; relative risk, 26.03; 95% confidence interval, 2.64 to 256.73; P = 0.005 for dialysis therapy), and mean proteinuria during follow-up (for each 1 g/d of protein increase, relative risk, 1.77; 95% confidence interval, 1.35 to 2.32; P0.001 for creatinine level doubling; relative risk, 1.73; 95% confidence interval, 1.18 to 2.52; P = 0.005 for dialysis therapy). Information for mean proteinuria levels during follow-up increased the sensitivity at logistic regression to 62.5%, with dialysis therapy as the end point. No data detected at diagnosis, including renal function impairment, proteinuria, hypertension, and crescentic nephritis (involving50% of glomeruli in only 2.6%), were significantly related to functional decline at multivariate Cox.This analysis indicates that, even more than when decreased renal function, severe proteinuria, hypertension, or crescents are present at onset, the risk for progression of HSPN (greater in adults and females) was associated with increasing mean proteinuria levels during follow-up.

The task of dialysis therapy is, amongst other things, to remo ve 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.

Enzyme replacement therapy with agalsidase beta in kidney transplant patients with Fabry disease: A pilot study. Background We sought to assess the safety and efficacy of enzyme replacement therapy (ERT) with recombinant human-α-galactosidase A (rh-α-Gal A) in kidney transplant recipients with Fabry disease, a previously unstudied population. Methods Three male kidney transplant recipients with biochemically, genetically, and histologically confirmed Fabry disease and documented Fabry myocardiopathy received the rh-α-Gal A, agalsidase beta, 1mg/kg of body weight every 2weeks by intravenous infusion and were monitored biochemically, clinically, and electrocardiographically and echocardiographically for 18months. Results Patients showed biochemical, clinical/functional, and morphologic response to ERT. Plasma globotriaosylceramide decreased 23% to 50%. Extremity pain resolved within 2months in the patient with this manifestation. On echocardiography, left ventricular mass, end diastolic diameter (EDD), and cardiac contractility, shown by ejection fraction (EF), improved in 2 of the 3 patients receiving essentially all planned infusions. EDD and EF remained basically stable, but cardiac morphologic abnormalities progressed in the other patient, who had a 5-month interruption in ERT after the initial month. Mild mitral insufficiency persisted in all patients, as did atrial fibrillation in the affected individual. After a combined total of 116 infusions, no treatment-related adverse event, intolerance, or seroconversion was seen. Renal function remained stable and the immunosuppression regimen unchanged in all patients. Conclusion Our pilot study provides preliminary evidence that ERT with agalsidase beta, 1mg/kg every 2weeks, is safe and often effective against extra-renal manifestations in kidney transplant patients with Fabry disease. Studies with longer courses of this and higher doses of ERT are merited in this population.

Focal glomerulosclerosis in patients with unilateral nephrectomy. To investigate whether proteinuria and focal glomerulosclerosis (FSG) might develop in humans as well as in experimental models following a reduction in renal mass, we performed a retrospective study of 24 patients previously nephrectomized for unilateral renal disease. None of the patients presented signs of systemic diseases, Alport syndrome, essential hypertension, reflux nephropathy, and other abnormalities on intravenous pyelography. At the time of the first observation seven patients had pathological proteinuria (group 1) while 17 presented a normal protein excretion (group 2). All patients in group 1 and only 4 of 17 in group 2 were male. No other significant differences were found between the two groups. The median age at nephrectomy of the proteinuric patients was 22.3 years, and proteinuria developed after a mean period of 12.2 years. A renal biopsy was performed in four patients and showed a constant pattern of FSG. After a mean follow-up period of 7.3 years from the onset, proteinuria remains unchanged and renal function is well preserved in all the patients. In conclusion our series suggests that also in humans proteinuria and FSG might appear in solitary kidneys due to nephrectomy. This glomerular damage may result from the association of glomerular overload with other unidentified factors. Glomerulosclerose focale chez des malades avec une nephrectomie unilaterale. Afin de rechercher si une proteinurie et une glomerulosclerose focales (FSG) peuvent se developper chez les humaines et dans des modeles experimentaux apres une reduction de la masse renale, nous avons effectue une etude retrospective de 24 malades nephrectomises auparavant pour une maladie renale unilaterale. Aucun de ces malades n'avait de signe de maladie systemique, de syndrome d'Alport, d'hypertension essentielle, de nephropathie de reflux ou d'autre anomalie a l'urographie intraveineuse. Au moment de la premiere observation, sept malades avaient une proteinurie pathologique (groupe 1) tandis que 17 avaient une excretion proteique normale (groupe 2). Tous les malades du groupe 1, et seulement 4 de 17 du groupe 2 etaient des hommes. Aucune autre difference significative n'a ete trouvee entre les deux groupes. La mediane de l'âge au moment de la nephrectomie des malades proteinuriques etait de 22,3 ans et la proteinurie se developpait apres une periode moyenne de 12,2 ans. Une biopsie renale a ete effectuee chez quatre malades et a montre un aspect constant de FSG. Apres un suivi moyen de 7,3 annees a partir du debut, la proteinurie reste inchange et la fonction renale est bien preservee chez tous les malades. En conclusion, nos series suggerent que chez les humaines egalement une proteinurie et une FSG peuvent apparaitre dans des reins solitaires apres nephrectomie. Cette lesion glomerulaire pourrait resulter de l'association d'une surcharge glomerulaire avec d'autres facteurs non identifies.

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

We conducted a controlled trial to investigate the long-term effects of treatment with methylprednisolone and chlorambucil in patients with idiopathic membranous nephropathy. We have previously reported that after a mean of 31 months, treated patients did better. We now report the results of a longer follow-up. Eighty-one patients with proteinuria (greater than or equal to 3.5 g per day) and biopsy-proved membranous nephropathy were randomly assigned to receive either supportive therapy alone or a six-month course of corticosteroids alternated with chlorambucil (0.2 mg per kilogram of body weight per day) every other month. Methylprednisolone was first given intravenously in three pulses (1 g per day) and was then given orally (0.4 mg per kilogram per day) for 27 days. The patients were followed for 2 to 11 years (median, 5). Two patients in the control group and one in the treatment group died. At the last follow-up visit, 9 of 39 patients assigned to the control group (23 percent) and 28 of 42 patients assigned to the treatment group (67 percent) did not have the nephrotic syndrome. At five years there were more remissions of the nephrotic syndrome in treated patients than in controls (22 of 30 vs. 10 of 25; P = 0.026). Compared with base-line values, the mean reciprocal of the plasma creatinine level declined significantly in the control group (33 percent; P = 0.0002) but not in the treatment group (6 percent; P not significant). Plasma creatinine increased by 50 percent or more in 19 controls (49 percent) and in 4 treated patients (10 percent). We conclude that a six-month course of methylprednisolone and chlorambucil can bring about sustained remission of the nephrotic syndrome and help to preserve renal function in patients with idiopathic membranous nephropathy.

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.

Model-based study of the effects of the hemodialysis technique on the compensatory response to hypovolemia.BackgroundHemodialysis technique (dialysate composition, filter, convection/diffusion ratio, etc.) can have an impact on the patient's tendency to acute hypotension. We have examined the hypothesis that the dialysis technique affects the hypotension risk by altering the cardiovascular compensatory response to hemodialysis-induced hypovolemia.MethodsTwelve hypotension-prone subjects were studied during six sessions of conventional bicarbonate dialysis (BD) and six sessions of acetate-free biofiltration (AFB). Blood volume (BV) control system was used in AFB to provide a BV change equivalent to the BV change observed in BD. The efficacy of reflex compensatory mechanisms was assessed by a model-based computer analysis of the BD and AFB sessions.ResultsBD sessions were complicated by hypotension more frequently than the AFB ones (34/66BD vs. 18/66AFB). Hypotension arose about 60 minutes earlier in BD (123 ± 41 minutes in BD vs. 183 ± 25 minutes in AFB, P < 0.01), and after a smaller BV reduction (hypotension BV 7.9%± 2.0% in BD vs. 10.9%± 2.6% in AFB, P < 0.05). Model-based computer analysis of the sessions without hypotension revealed differences in peripheral resistance adaptation (9%± 9% BD vs. 19%± 7% AFB, P < 0.05) as well as in the stroke volume reduction (19%± 8% BD vs. 10%± 8% AFB, P < 0.001). Model analysis of sessions with hypotension indicated that compensatory mechanisms were almost inoperative in BD, whereas a residual capacity to control peripheral resistance and cardiac contractility was present in AFB. Model simulations demonstrated that hypotension occurred later in AFB since the residual compensatory capacity in AFB was able to sustain the arterial pressure for larger BV reductions (8.3% BD vs. 11.2% AFB).ConclusionThe increased risk of acute hypotension in BD compared to AFB is caused by a therapy-induced inhibition of reflex compensatory response to hypovolemia.

SUMMARY Twenty-five patients with diffuse proliferative lupus nephritis were treated with three consecutive Intravenous injections of 1 g methylprednisolone pulses followed by small doses of prednisone. These patients were followed for at least three months. Major side-effects were observed only in one patient. After steroid administration, extrarenal symptoms rapidly disappeared in all patients. Except for four patients with diffuse glomerular sclerosis a significant improvement of serum creatinine was observed after one month and the improvement was more sustained after three months. No deterioration was observed in patients with normal functioning kidneys. Proteinuria decreased significantly over three months. When tested, anti-dsDNA binding capacity and serum complement components became normal within four weeks. Seventeen patients were then followed for 12–93 months. Ten patients received only small doses of oral prednisone and seven were also treated with cytotoxic agents. Eight ‘flare-ups’ of disease occurred in these patients over a cumulative period of 688 months. Additional steroid pulses were administered during the ‘flare-ups’, with subsequent improvement of symptoms and renal function in all but one patient, who had diffuse glomerular sclerosis at biopsy. At present the mean values of serum creatinine are lower than baseline values. One patient has renal failure and another one has moderate renal insufficiency. No patient has the nephrotic syndrome and six patients are free from proteinuria. We suggest that aggressive treatment based on short-term intravenous methylprednisolone during relapse followed by a low-dose maintenance regimen may be a safe and effective way to manage most patients with diffuse lupus nephris.

We retrospectively studied 82 consecutive patients with idiopathic membranous nephropathy accepted at two separate Renal Services. These patients had nephrotic syndrome at presentation and had been followed up for at least 10 years. The duration of the disease before renal biopsy ranged between 1 and 18 months. Forty-nine patients never received treatment (non-treated group) whereas 33 patients (treated group) received corticosteroids (and cytotoxic agents). The two groups were age and sex matched. There was no difference in clinical findings or in outcome between the two Renal Services. A complete and sustained remission of proteinuria was observed in about 25% of patients, and there was a significant difference (P less than 0.01) between the treated and non-treated group (mean value 39.1% vs 14.3%). Forty-four per cent of the non-treated patients and 24.2% of the treated ones developed chronic renal failure or renal death during a mean potential follow-up of 14 years. Non-renal death was recorded in 19.5% of the patients. The staging of the capillary wall lesion represented a very important prognostic index. We confirm, therefore, that idiopathic membranous nephropathy with nephrotic syndrome is frequently a progressive disease. Corticosteroids (and cytotoxic drugs) seem to be of some benefit in interfering with the natural course of the disease.

In 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 response in vitro. Moreover, the diminished lymphocyte responsiveness to mitogens during pregnancy seems to be due to humoral circulating factor(s).