Use of autologous bone marrow cells concentrate enriched with platelet-fibrin on extensor mechanism allograft reconstruction for extensor mechanism failure following total knee arthroplasty.

Allografts techniques remain the best reconstructive strategy for chronic extensor mechanism lesions after total knee arthroplasty (3) but outcomes depend strictly on the host tissue-allograft junctions healing. The purpose of this study is to evaluate if modern techniques of adding autologous bone marrow cells concentrate enriched with platelet-rich fibrin, provide better healing of the allograft. We present the case of an 86 years old patient affected by patellar tendon rupture after TKA. A whole extensor mechanism allograft was performed adding a bone marrow cells concentrate enriched with platelet-rich fibrin on the host tissue-allograft junctions. Preoperatively and at each follow-up the value of Knee Society Score and radiographic consolidation signs were recorded. Radiographic controls showed clear signs of consolidation already at 1 months follow-up and a solid fusion at 3 months. This case report describes a valid method to improve healing using a tissue-construct engineered with stem cells and growth factors.

[Italian Registry of Dialysis and Transplantation: 1996-2001 experience]. / Registro Italiano Dialisi e Trapianto. Esperienza 1996-2001.

The Italian Registry of Dialysis and Transplantation (RIDT) was born in 1996 under the aegis of the Italian Society of Nephrology, and it is organized as a federation of regional registries. This study aimed to completely revise the epidemiological data collected during the first 5 yrs (1996-2001) of RIDT activity to evaluate the trends of the main epidemiological features. During this period, regional registries were not always able to assure complete and exhaustive information according to RIDT requirements, owing to different levels of organization and functioning. To avoid any possible error in data analysis, information inadequately assessed was refused. The incidence of end-stage renal disease (ESRD) patients on renal replacement therapy (RRT) in Italy has increased from 114 pmp in 1996 to 139 pmp in 2001, that means an increase of 3.5%/yr, corresponding to 5718 patients during 1996 and 8000 patients during 2001. Primary renal diseases (according to the EDTA) in incident ESRD patients are vascular and diabetic nephropathy. Main dialysis modality in incident patients was hemodialysis (HD) (85%), while peritoneal dialysis (PD) was only 15%; pre-emptive transplantation was a very unusual modality. The prevalence of ESRD patients at 31 December was 693 pmp in 1996 and 827 pmp in 2001; among dialysis patients, the corresponding rates were 575 pmp and 657 pmp, respectively. Consequently, the number of dialyzed patients increased, respectively, from 28892 to 37919. The prevalent dialysis modality was bicarbonate dialysis in 74% of cases, followed by hemodiafiltration (HDF) in 15%, continuous ambulatory peritoneal dialysis (CAPD) in 7% and APD in 3%. The gross mortality rate in dialyzed patients was stable during this period, at approximately 14%, the main causes of death being cardiovascular diseases and cachexia.

[Alterations of cardiac output during bicarbonate hemodialysis and its relationship with other hemodynamic parameters]. / Modificazioni della gittata cardiaca durante emodialisi con bicarbonato e sue relazioni con altre variabili di pertinenza cardiologica.

PURPOSE: Time course of cardiac output (CO) and other hemodynamic parameters were measured during hemodialysis (HD). Our aims were to identify a characteristic CO profile and investigate the relationship with other hemodynamic parameters. PATIENTS AND METHODS: CO was measured with ultrasound dilution method in 45 chronic hemodynamically stable HD patients. Diabetics and patients with heart diseases were excluded. Ultrafiltration rate (UFR) was fixed at 649 +/- 244 mL/min. Pre/post statistical comparisons were performed for CO, cardiac index (IC), central blood volume (CBV) and total peripheral resistance (TPR). RESULTS: CO was pre 5.7 +/- 1.8 and post 4.5 +/- 1.4 L/min (p=0.001); IC was pre 3.2 +/- 0.9 and post 2.6 +/- 0.7 L/m2 (p=0.001); CBV was pre 1.28 +/- 0.39 and post 1.09 +/- 0.32 L (p=0.001). TPR increased from 18.7 +/- 5.6 to 22.7 +/- 6.1 mmHg/L/min (p=0.001). Maximal CO reduction rate was found at 60 min, thereafter it reduced progressively. Log(CO1) increased in a non-linear way with body weight gain and similarly it decreased during UFR. A negative correlation was found between log(TPR1) and log(CO1-QA). CO reduction was associated with UFR and not with age, dialysis duration, left ventricular hypertrophy, sex and hemoglobin (Hb) in a multiple regression model (r2 =0.31, p=0.05). Qa/CO1 was 0.16 +/- 0.12. CBV/CO increased from 0.23 +/- 0.06 to 0.25 +/- 0.07%. CONCLUSIONS: Progressive CO reduction and TPR increase appear to be the typical hemodynamic features of bicarbonate HD with a UFR of moderate degree. Volume overload and CO increase were related in a non-linear way. TPR1 was strongly correlated with CO1-Qa, suggesting that a large arterovenous shunt was associated with increased resistance.

Continuous urea monitoring in hemodialysis: a model approach to forecast dialytic performance. Results of a multicenter study.

BACKGROUND: A urea biosensor, inserted into the ultrafiltrate collection-line of paired filtration dialysis (PFD), not only allows on-line dialysis quantification, but also forecasts final (Cend) and 30 min equilibrated urea concentration (Ceq), the most reliable value for calculating dialysis efficiency. The urea biosensor processes plasma ultrafiltrate continuously, delivering a large amount of data to the computer, which estimates the parameters by a mathematical model, thus predicting the whole urea profile with rebound. METHODS: A multicenter randomized trial on 41 patients was conducted to ascertain the ability of a two-pool variable-volume urea model to forecast Cend and Ceq at 60 and 90 min after the start of dialysis. Two alternative dialytic treatments, A or B, were chosen, the latter being more efficient. Each treatment included six serial PFD. The accuracy of forecasting was evaluated through four indices based on forecast errors, calculated as the difference between observed and forecasted urea values: mean percent error (MPE) (%), mean absolute deviation (MAD) (mg/dl), mean absolute percent error (MAPE) (%) and root mean squared error (RMSE) (mg/dl). RESULTS: Forecasted urea concentrations were lower than those measured by the biosensor. MPE for Cend was negligible in A (+1.2%) and much higher in B (+7.2%); both values improved at 90 min, +1.0% and +5.8%, respectively. MAD for Cend was similar in both treatments and improved slightly at 90 min, ranging from 4.9 to 5.9 mg/dl. MPE for Ceq was +4% in A and and more than doubled in B (+11.5%); both values improved at 90 min, +3.7% and +9.7%, respectively. MAD for Ceq was 7.5 mg/dl in A and 8.5 mg/dl in B; both improved at 90 min, 6.7 and 7.4 m g/dl, respectively. The other indices, MAPE and RMSE, showed similar results. Comparison between the errors of the two treatments with analysis of variance (ANOVA) for repeated measures gave no significant results. CONCLUSIONS: Our model forecasts of urea concentrations were overall lower than the measured ones: the bias was negligible for A-Cend, greater for the A-Ceq and when the more efficient treatment B was used. The 60 min predictions improved at 90 min. The comparison between the prediction errors in the two treatments were not statistically significant. The recirculation measurement would probably reduce the bias if it were properly incorporated into the model.

Adequacy in hemodialysis: new concepts derived from online urea monitoring.

BACKGROUND: The estimation of urea kinetic parameters [urea generation rate (Gu), normalized protein catabolic rate (NPCR), and dialysis dose (Kt/V)] is routinely performed during a single hemodialysis session as a representative sample of a stable series. To ascertain whether the stability assumption is tenable and to estimate the variability of urea kinetic parameters, a number of stable patients on regular dialysis treatment in their usual clinical setting were followed. METHODS: Thirteen stable patients on regular hemodialysis aged 61 +/- 11 were monitored from 5 to 24 weeks (median, 10 weeks) with the urea biosensor system in double-chamber hemodiafiltration. Body weight did not change appreciably. Residual renal function was negligible or absent. Weekly averaged urea concentration (TACw), Gu, NPCR, and Kt/Veq were calculated, and their serial patterns and interrelationships were evaluated through graphical analysis and linear regression. RESULTS: In six patients, the urea pool was substantially unchanged, but variability of Gu and Kt/V was comparable to that of the other groups. In three patients, body urea pool increased. Gu went from 4. 78 +/- 0.44 to 5.40 +/- 0.65 mg/min, and Kt/V went from 1.25 +/- 0. 25 to 1.34 +/- 0.31. In four patients, body urea pool decreased; Gu went from to 6.55 +/- 1.91 to 5.85 +/- 2.26 mg/min, and Kt/V did not change appreciably. Parameters might change in a nearly linear trend or occasionally as abrupt or oscillating phases. Gu was the main factor involved, and the only one affecting four of the seven unstable patients. Kt/V was never solely involved. CONCLUSIONS: Our data indicate that the estimation of urea kinetic parameters is often affected by a non-negligible degree of variability, which can be ascribed to the variability of the dialytic dose delivered and, above all, to the daily changes of diet protein assumption.

On-line urea kinetics in haemodiafiltration.

BACKGROUND: Calculation of Kt/V and assessment of nutrition have so far been dependent upon off-line urea measurements of blood or dialysate samples. Here we describe a biosensor for on-line urea measurement during haemodiafiltration. Methods. The biosensor consisted of a cartridge containing covalently linked urease placed between two conductivity cells. The biosensor was placed on the outlet line of a haemofilter in series with a dialyser in order to obtain an aliquot of plasma ultrafiltrate for on-line measurement of urea. RESULTS: Urea nitrogen concentrations were highly correlated to the difference (Delta) in conductivity measured by the two conductivity cells both in aqueous solutions (in-vitro studies, y=-6. 676+32.12x, R2=0.998, P<0.0001) and in ultrafiltrates (ex-vivo studies, y=-637+32.01x, R2=0.98, P<0.00001). Delta conductivity was highly reproducible (% variation: ).8-5.3%) and stable (maximal % variation at 150 mg/dl after 100 min. 0.9+/-0.3 vs initial values). The intradialytic plasma water urea profile was obtained in 10 haemodialysis patients. To study recirculation, the plasma water urea profile was analysed before and 3 min after stopping the dialysate flow. The pre- and post-stopped flow ratio (1.21+/-0.1, mean+/-1 SD) was superimposable to conventional blood sampling data (opposite arm venous arterial: 1.22+/-0.11) and allowed correction for recirculation. A novel approach to urea kinetic modelling was described and used to reliably project end-dialysis and post-dialysis rebound urea concentration as early as 90 min. Projected (29.2+/-10.4 g) or measured (29.8+/-10.5 g) net urea removal was highly correlated with the amount of urea collected in the total spent dialysate (29.7+/-10.6 g) (R2=0.99, R2=0.97 respectively). CONCLUSIONS: These results indicate that on-line, real-time analysis of urea kinetics may provide information on delivery of adequate dialysis in high-efficiency techniques.

Blood volume modeling and refilling rate estimation in hemodialysis by continuous hemoglobin monitoring.

Eleven bicarbonate hemodialyses (HD) of 6 patients under constant ultrafiltration were continuously monitored with an optical Hb-meter, considered to be a marker of blood volume (BV) changes. A theoretical model was fed experimental data for prediction of blood volume and estimation of vascular parameters, and a time course of rate of refilling was extrapolated. The adequacy of the model was very good for the time course of BV prediction (r2 = 0.85-0.95, n = 11) and for plasma protein concentration (r2 = 0.83-0.86, n = 2). Parameters estimated included (mean-DS): filtration coefficient (Cf) = 0.22 (0.16) dl/min*mmHg, transcapillary hydrostatic pressure (DP) = 17.80 (3.44) mmHg and protein concentration of the refilling fluid (Cref) = 0.45 (0.30) g/dl. In conclusion our study has shown that the model chosen fits the observed BV profile well in all cases, thus the Hb data series can be used for BV dynamic modeling and for estimation of vascular parameters.

Biochemical aspects and clinical perspectives of continuous urea monitoring in plasma ultrafiltrate. Preliminary results of a multicenter study.

We tested a new biosensor for urea monitoring in the ultrafiltrate during PFD in a group of 5 hemodialyzed stable patients. The inspection of the UF-urea profile reflects the dynamical changes of the plasma urea concentration during diffusive dialysis and allows the fitting of the main mathematical models of urea kinetics. The biosensor efficiency was 98.4% on average (SD: 1.5%) at Uf fluxes varying from 45 to 55 ml/min (mean: 51 ml/min; SD: 3.2) and at Uf-urea concentrations varying from 23 to 165 mg/dl. The mean difference between Uf-urea determined by the laboratory method and Uf-urea assayed by the biosensor was -1.07 mg/dl and the 95% confidence interval ranged from -2.01 to 0.13 mg/dl. The mean difference between laboratory plasma urea and Uf-urea from the biosensor was on average -1.9 mg/dl and the estimated limits of agreement with a confidence of 95% were -3.16 and 0.64 mg/dl. Comparison between kinetic models and experimental profiles of plasma urea decrease, evaluations of recirculation and post-dialytic rebound, the role of Kt/V on-line during dialysis were the preliminary clinical applications of this biosensor.

Long-term predictors of survival in essential mixed cryoglobulinemic glomerulonephritis.

We report the clinical outcome of 105 essential mixed cryoglobulinemia (EMC) patients with renal involvement collected throughout 25 years in three renal Units of Milan. The median follow-up was 72 months since renal biopsy and 131 months since the clinical onset of EMC. Patient survival was 49% at 10 years after renal biopsy. Forty-two patients died primarily from cardiovascular and liver disease or infection, whereas 15 patients developed chronic renal failure. Two patients had a complete remission of the disease while 15 had a remission only of renal signs. Thirty-one patients are alive with persistent renal and extrarenal manifestations. Anti-HCV antibodies were retrospectively detected in 34 patients and were present in 85% of them. This variable was not included in the statistical evaluation. At multivariate analysis, age older than 50 years, purpura, splenomegaly, cryocrit levels higher than 10%, C3 plasma levels lower than 54 mg/dl, and serum creatinine higher than 1.5 mg/dl were independent risk factors for death or dialysis. In conclusion, several factors may influence the outcome of patients with EMC nephritis. Markers of disease activity and an impaired renal function can herald a bad prognosis. It should be stressed, however, that only a minority of patients eventually develop renal failure, probably because in the most severe cases patients die earlier.

The clinical significance of IgA rheumatoid factor in idiopathic IgA mesangial nephropathy (Berger's disease).

IgA rheumatoid factor, IgA and IgG immune complexes were measured in 119 patients with IgA nephropathy. IgA rheumatoid factor was detected in 62/119 (52%) patients and in 92/265 (35%) serum samples. There was a good correlation (p less than 0.001) between the presence of IgA rheumatoid factor and the presence as well as levels of IgG immune complexes, but not between levels of IgA rheumatoid factor and other clinical or immunological parameters. However, higher levels of serum IgA were found in the subgroup of patients with constantly positive IgA rheumatoid factor. Using aggregated human IgG, we could not demonstrate antiglobulin activity in renal biopsy specimens from 36 patients. These results suggest that IgA rheumatoid factor does not play a primary role in renal damage in IgA nephropathy, but could simply reflect a response to IgG immune complexes in a disorder characterized by abnormalities of IgA production. Nevertheless, the presence of circulating IgA rheumatoid factor in a substantial proportion of patients, especially in those with features of polyclonal IgA activation, provides additional evidence for a general perturbation of IgA metabolism in this disease and could represent an antigen-specific system with which to study regulation of IgA synthesis.

Characterization of interstitial infiltrating cells in Berger's disease.

The role of infiltrating blood-borne cells in the pathogenesis of renal damage in human glomerulonephritis is under active investigation. We have evaluated leukocyte infiltrates (number of cells/mm2) in the renal interstitium of 21 patients with Berger's disease and eight normal kidneys with monoclonal antibodies and a four-layer immunoperoxidase technique. In our population of patients, the number of infiltrating T-lymphocytes (OKT11+ cells) was significantly higher (median, 132) than in the normal kidneys (median, 60). This increase was mainly due to T-suppressor/cytotoxic lymphocytes (OKT8+ cells; median, 68), while T-helper/inducer lymphocytes (Leu 3A+ cells) and monocytes were in the normal range. T-lymphocyte infiltration was more marked in ten patients with impaired glomerular filtration rate (GFR) at the time of biopsy (median, 167) than in patients with normal GFR (median, 88). In addition, ten patients who showed deterioration of renal function during the subsequent follow-up, whatever their serum creatinine levels at the time of biopsy, had significantly more total T cells (median, 269), OKT8+ cells (median, 143), and Leu 3A+ cells (median, 105) than 11 patients with persistently stable GFR and normal controls. More data are necessary to establish whether this T-lymphocyte infiltration is the consequence of a cell-mediated mechanism acting in the interstitium, concomitant with the immune-complex-mediated mechanism acting in the glomerulus, or is a nonspecific consequence of the tubulointerstitial damage induced by the immunologically mediated glomerular disease.

Food antigens, IgA-immune complexes and IgA mesangial nephropathy.

To investigate whether patients with IgA nephropathy have an exaggerated serum IgA response to ubiquitous food antigens we measured serum IgA antibodies to gliadin, ovalbumin, bovine serum albumin (BSA), beta-lactoglobulin and casein in 120 patients and 53 normal controls, using ELISA. No significant differences were observed between patients and controls in serum IgA antibodies against each of the antigens tested. Moreover, no correlation was found between serum IgA antibodies and IgA-immune complexes (IgA CIC). However, nine patients but no controls had an association of two or more IgA antibodies to dietary antigens. Sixty-six per cent of these patients (vs 24% in the remaining population) had IgA CIC, suggesting a possible involvement of these antibodies in the constitution of IgA CIC. Analysis of sera by HPLC revealed that both monomeric and higher molecular forms of IgA antibodies were present, the latter being coincident with the peak of IgA CIC. Preincubation of sera with serial concentrations of the specific antigen decreased significantly IgA CIC, suggesting that in this subgroup of patients IgA antibodies to food antigens (mainly BSA) are involved in the formation of IgA CIC. BSA-containing IgA CIC were in fact demonstrated by ELISA using rabbit IgG anti-BSA coated plates and peroxidase-conjugated anti-human IgA. The role of these CIC in the pathogenesis of IgA nephropathy needs to be further elucidated.

Deposition of fibrin-stabilizing factor (F XIIIA and S), fibrinogen-related antigens, fibrinogen degradation products (FDPd and FDPe) and antihemolytic factor (F VIII) in renal disease: analysis of 161 cases by immunofluorescence microscopy.

To see whether or not the fibrin-stabilizing factor is involved in the pathogenesis of renal damage, we analyzed by IF the glomerular deposition of factor XIII (subunits A and S) in 161 patients with various renal diseases. In 4 out of 5 cases of thrombotic microangiopathy (80%), F XIII deposits were found in a continuous subendothelial pattern, in association with deposition of fibrinogen and FDP, suggesting the occurrence of intraglomerular coagulation. In 22 out of 45 patients with membranous GN (idiopathic or SLE-associated), F XIII deposits were found along the capillary walls in a subepithelial location. These findings were not correlated with the presence of particular histological or clinical features, nor with IF positive for fibrinogen, FDP and factor VIII, suggesting alternative pathways of fibrin formation or local collagen synthesis. Finally, in proliferative GN, either idiopathic (acute post-infectious and membranoproliferative) or systemic (SLE and vasculitis), as in other glomerular and non-glomerular diseases, the presence of F XIII deposits was negligible, even in cases positive for fibrinogen, FDP and factor VIII.