Incidence of late deep venous thrombosis among renal transplant patients.

BACKGROUND: Kidney transplant recipients (KTRs) manifest hypercoagulable state that contributes to an increased incidence of deep vein thrombosis (DVT), not only early but also late in their course. KTRs display an imbalance of hemostatic mechanisms with a multifactorial rise in procoagulant factors, partly related to traditional risk factors and partly to transplantation. The aim of this study was to evaluate the incidence of first episodes of DVT among KTRs, focusing on risk factors. METHODS: From 2008 to 2011, we evaluated 30 kidney transplant patients who ≥4 months there after transplantation developed DVT in the lower limbs only, lower limbs complicated by pulmonary embolism or retinal thrombosis. We analyzed causes of primary nephropathy, immunosuppressive regimen, post-transplantation infections, and erythrocytosis. DVT was diagnosed by color Doppler ultrasound or eye examination. RESULTS: A significantly increased incidence of DVT was observed among patients receiving cyclosporine or cyclosporine + mammalian target of rapamycin inhibitors, affected by polycystic kidney diseases, systemic lupus erythematosus or nephrotic syndrome, or displaying rapid and/or excessive correction of hematocrit values. DVT was not significantly related to an acute infection (cytomegalovirus) or to the prior dialysis modality. CONCLUSIONS: Hypercoagulability is a multifactorial condition in KTRs, representing a severe complication in stable patients. Prevention may consist of either accurate pretransplantation screening for thrombophilia or identification of patients at higher DVT risk.

Artificial kidney: status of the art and new perspectives.

Extracorporeal dialysis was first performed in 1943 and has become a routine for End Stage Renal Patients from the early sixties. In the last 30 years researchers have focused on biocompatibility of artificial materials and optimisation of removal of uremic toxins by the membrane as in the long term treatment many complications like amylodosis heart and bone lesions, accelerated amyloidosis and immune system failure can occur. From this point of view high flux dialytic membranes are currently considered more biocompatible therefore being able to prevent such diseases.

Evaluation of intradialytic solute and fluid kinetics. Setting Up a predictive mathematical model.

A mathematical model of solute kinetics for the improvement of hemodialysis treatment is presented. It includes a two-compartment description of the main solutes and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained in vivo during 11 different hemodialysis sessions performed on 6 patients with a profiled sodium concentration in the dialysate and a profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and the in vivo data proves fairly good as to urea, sodium, chloride, potassium and bicarbonate kinetics. Only in two sessions was blood volume directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and makes it possible to predict the plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve clinical tolerance to the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic hypotension.

Mathematical modeling of solute kinetics and body fluid changes during profiled hemodialysis.

A mathematical model of solute kinetics oriented to improve hemodialysis treatment is presented. It includes a two-compartment description of the main solutes (K+, Na+, Cl-, urea, HCO3-, H+, CO2), acid-base equilibrium through two buffer systems (bicarbonate and non-carbonic buffers) and a three-compartment model of body fluids (plasma, interstitial and intracellular). The main model parameters can be individually assigned a priori, on the basis of body weight and plasma concentration values measured before beginning the session. Model predictions are compared with clinical data obtained during 11 different hemodialysis sessions performed on six patients with profiled sodium concentration in the dialysate and profiled ultrafiltration rate. In all cases, the agreement between the time pattern of model solute concentrations in plasma and clinical data turns out fairly good as to urea, sodium, chloride and potassium kinetics. Finally, the time patterns of plasma bicarbonate concentration and pH can be reproduced fairly well with the model, provided CO2 concentration remains constant. Only in two sessions, blood volume was directly measured in the patient, and in both cases the agreement with model predictions was good. In conclusion, the model allows a priori computation of the amount of sodium removed during hemodialysis, and may enable the prediction of plasma volume changes and plasma osmolarity changes induced by a given sodium concentration profile in the dialysate and by a given ultrafiltration profile. Hence, it can be used to improve the dialysis session taking the characteristics of individual patients into account, in order to minimize intradialytic imbalances (such as hypotension or disequilibrium syndrome).

Clinical use of profiled hemodialysis.

The new population on dialysis today consists mainly of high risk patients (the elderly, diabetics, etc.) with high cardiovascular scores, and such vascular pathology is the most important predisposing factor for the occurrence of a frequent intradialytic clinical complication, vascular instability syndrome, which covers a range of clinical problems. Recently a new dialysis technique, profiled hemodialysis (PHD), has been set up and proposed for routine use. PHD consists of the clinical use of preestablished individual dialysis profiles aimed at antagonizing the changes in intradialytic plasma osmolarity by continuous modulation of dialysate sodium concentration throughout the whole extracorporeal session. In particular, PHD aims at reducing the fall of plasma osmolarity in the first half of the session (when it is higher) by reducing the sodium removal rate through increasing its dialysate concentration while taking into account the desired individual sodium balance to be reached at the end of the session. In this work, we report clinical experience with PHD compared to standard hemodialysis with constant sodium dialysate (SHD) in terms of its efficacy to maintain a more stable intradialytic blood volume (BV) and more stable hemodynamics. The PHD used in this work has been implemented by a mathematical model for computing the individual dialysate sodium profile which we have recently validated (Ursino M, Coli L, La Manna G, Grilli Cicilioni M, Dalmastri V, Guidicissi A, Masotti P, Avanzolini G, Stefani S, Bonomini V. A simple mathematical model of intradialytic sodium kinetics: "in vivo" validation during hemodialysis with constant or variable sodium. Int J Artif Organs 1996;19:393-403.). Eleven uremic patients affected by hypotension at the beginning of dialysis treatment were studied. Each patient first underwent an SHD treatment and 1 week later a PHD treatment. The 2 extracorporeal sessions (one on SHD and the other on PHD) were performed in each individual patient under identical operative conditions including the sodium mass removal by the end of the session and the ultrafiltration rate. The crit line and Doppler echocardiography were used to determine BV, cardiac output (CO), and stroke volume (SV) throughout the sessions. The mean blood pressure (MBP) and heart rate (HR) were simultaneously monitored. PHD was associated with a more stable intradialytic BV and more stable hemodynamics compared to SHD. The higher stability of BV and cardiac function (in terms of SV and CO maintenance) which was obtained above all in the first half of the PHD session was associated with a higher stability of the MBP and the HR. This resulted in an enhancement in cardiovascular tolerance to ultrafiltration throughout the session in all tested patients. In contrast, SHD in the same patients was characterized by early significant changes in BV and cardiovascular parameters resulting in a significant decrease of the MBP and a significant increase of the HR throughout the session and also 1 h after the end of dialysis. Our results indicate that PHD may represent an efficient approach for the treatment of patients suffering from intradialytic vascular instability. If long-term clinical practice confirms the efficacy of PHD in controlling dialysis intolerance symptoms, it will have great scope as a routine procedure.

Evidence of profiled hemodialysis efficacy in the treatment of intradialytic hypotension.

In the last 10 years the percentage of dialysis patients suffering from clinical intradialytic intolerance has greatly increased. Profiled hemodialysis (PHD) is a new technical approach, alternative to standard hemodialysis (SHD) for the treatment of intradialytic symptomatic hypotension. It is based on intradialytic modulation of the dialysate sodium concentration, using a dialysate sodium concentration profile elaborated by a new mathematical kinetic model. The aim of PHD is to reduce the intradialytic blood volume decrease, thanks to a dialysate sodium profile, which allows a reduction in the plasma osmolarity decrease, thereby boosting intravascular fluid refilling. This work aims at clinically validating the PHD technique, by testing its ability against SHD, to maintain a more stable intradialytic blood volume; this evaluation was supported by monitoring some hemodynamic parameters. Twelve dialysis patients on SHD treatment were selected because of their intradialytic symptomatic hypotension. Twelve SHD (one per patient) and 12 PHD sessions (one per patient) were performed to achieve the same sodium mass removal and body weight decrease on both PHD and SHD. During these sessions we monitored the blood volume variation % by the crit-line (a non invasive blood volume monitoring device), the mean blood pressure and heart rate directly and, finally, the stroke volume and cardiac output indirectly by bidimensional doppler-echocardiography. Comparison of the results obtained with the two techniques shows PHD to achieve a significantly more stable blood volume, blood pressure and cardiovascular function than SHD, in particular during the second and the third hour of the dialysis session.

A simple mathematical model applied to selection of the sodium profile during profiled haemodialysis.

BACKGROUND: Among dialysis patients in the last 10 years the incidence of intradialytic dysequilibrium syndrome and symptomatic hypotension has increased significantly. Profiled haemodialysis (PHD), a new dialysis technique based on intradialytic modulation of the dialysate sodium concentration according to pre-elaborated individual profiles, has been set up to reduce intradialytic imbalances and the incidence of dysequilibrium syndrome and symptomatic hypotension. The present paper illustrates a new mathematical model for solute kinetics, single-compartment for sodium and two-compartment for urea, aimed at improving the use of PHD. The model allows the sodium profile to be elaborated a priori, before each dialysis session, according to the patient's clinical needs and respecting the individual sodium mass removal and weight gain. METHOD: The mathematical model was first derived and then applied to determining a rational dialysate sodium profile. A procedure which allows the method to be tuned to individual clinical needs on the basis of routine measurements performed before each session is also presented. The proposed method was validated in vivo during seven dialysis sessions, each performed on a different patient. RESULTS: The comparison between data predicted by the model and those obtained in vivo shows a good correspondence in particular concerning the time pattern of blood urea and sodium. The comparison between the model prediction and in vivo determined sodium and urea plasma curves showed standard deviations (2.25 mEq/l for sodium and 0.87 mmol/l for urea) only slightly higher than those attributable to laboratory measurement errors. Moreover, in vivo implementation of PHD by our model enables one to remove an amount of sodium mass comparable with the a priori quantity predicted by the model.

An algorithm for the rational choice of sodium profile during hemodialysis.

The incidence of intradialytic disequilibrium syndrome and symptomatic hypotension has increased significantly among dialysis patients over the last ten years. Profiled hemodialysis (PHD) is a new technique, based on the intradialytic modulation of dialysate sodium concentration, which aspires to reduce to previous imbalances. This paper presents a new algorithm for the determination of a rational dialysate sodium profile during PHD. A mathematical model of solute kinetics, monocompartmental for sodium and bicompartmental for urea is used. The algorithm allows the sodium profile to be elaborated a priori before each dialysis session, respecting the individual sodium mass removal and weight gain. A procedure allowing the adjustment of the method to the individual characteristics, on the basis of routine measurements performed before each session is also presented. The method was validated during seven dialysis sessions. Comparison between data measured in vivo and those predicted by the model showed standard deviations corresponding to the range of laboratory measurement errors: 1.50 mEq/L for sodium and 0.87 mmol/L for urea. In vivo implementation of PHD by our algorithm allows one to remove an amount of sodium close to that established a priori on the basis of patient's need.

A simple mathematical model of intradialytic sodium kinetics: "in vivo" validation during hemodialysis with constant or variable sodium.

A simple mathematical model of the intradialytic relationship between natraemia and dialysate sodium concentration is presented. The model includes a bicompartmental description of sodium, urea and fluid kinetics and an algebraic characterization of diffusive/convective mass-transfer across the dialysis membrane. Its ability to provide realistic responses has been validated comparing model predictions by a priori parameter tuning against quantities measured during in vivo sessions with both constant and variable dialysate sodium concentration. A quantitative analysis of model predictions indicates that the mean deviation between data calculated by the model and those measured in vivo is 1.32 mEq/l for sodium and 0.76 mmol/l for urea, values which do not greatly exceed the measurement errors of current instruments. The model's predictive capacity thus proves reliable. The ability of the model to calculate the amount of sodium removed and the time course of intra-extracellular volumes during the dialysis session makes it possible to forecast the patient's clinical tolerance to a given sodium dialysate concentration.

Posttraumatic chyluria due to lymphorenal fistula regressed after somatostatin therapy.

A sudden-onset chyluria after trauma was evaluated giving evidence of a lymphatic-urinary fistula in the right kidney. Treatment with somatostatin normalized the urinary pattern and the result was maintained even after the discontinuation of the therapy.

Is Ace inhibitor treatment a possible cause of better cardiovascular remodelling in well functioning kidney transplant?

Diseases of the cardiovascular system are a common cause of death in renal transplanted patients. In this study we assessed the echocardiographic morphological and functional findings after renal transplantation of two homogenous groups of transplanted patients with normal renal function. The first (A) with spontaneously normotensive patients, the second (B) with moderate hypertension treated mainly with Ace inhibitors. Analysis of these data highlights two noteworthy results: the similar left ventricle hypertrophy found in both groups and the existence of better diastolic compliance among the hypertensive transplanted patients. If this is confirmed by studies currently in progress, the importance of Ace-inhibitors treatment in remodelling cardiac dysfunction after long term dialysis treatment might be seriously considered.