Giovanni Mosconi

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, HCO–3, 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).

Serum Alpha-1-Acid Glycoprotein in Chronic Renal Failure

We measured the serum concentration of alpha-1-acid glycoprotein (AAG) in 30 healthy subjects (controls), in 54 patients with various degrees of residual renal function (group I), and in 98 patients in the terminal phase of chronic renal failure (CRF) on both conservative and dialytic therapy (group II). A positive correlation between the logarithm of serum AAG and serum creatinine levels was found in group I. Serum AAG increased significantly when serum creatinine rose above 10 mg/dl. This fact would indicate that a retention of the substance occurs as the renal function falls. The mean serum concentration of AAG was significantly higher in group II patients, with no difference between those on conservative therapy and those on maintenance hemodialysis. However, levels above normal were present in only a minority of cases. We conclude that the serum AAG measurement maintains its diagnostic value as an acute phase reactant also in the terminal phase of CRF.

Epidemiology of Hepatitis C in a Population of Hemodialysis Patients

A search for antibodies against hepatitis C virus (HCV) was performed in 185 patients on chronic hemodialysis by means of 1st and 2nd generation ELISA tests. Immunoblot assays were performed on positive sera. This study shows a 38% prevalence of HCV-positive patients in our dialysis population according to the 2nd generation ELISA test which shows a higher specificity and sensitivity when compared to the 1st generation one (38 vs. 20%). A correlation was found between the prevalence of HCV-positive patients and how long they had been on dialysis and how many blood transfusions they had received.

A clinical stratification tool for chronic kidney disease progression rate based on classification tree analysis

BACKGROUND Registry-based studies have identified risk factors for chronic kidney disease (CKD) and for progression to end-stage renal disease. However, usually, these studies do not incorporate sequential measurements of kidney function and provide little information on the prognosis of individual patients. The aim of this study is to identify which combinations of demographic and clinical characteristics are useful to discriminate patients with a differential annual decline in glomerular filtration rate (GFR). METHODS This observational retrospective study includes patients enlisted in the registry of the Prevention of Progressive Renal Insufficiency Project of Emilia-Romagna region (Italy) from July 2004 to June 2010, with at least four serum creatinine measurements. Classification tree analysis (CTA) was used to identify subgroups of patients with a different annual GFR decline using demographic and laboratory data collected at study entry. RESULTS The CTA procedure generated seven mutually exclusive groups. Among patients with proteinuria, those with a baseline estimated GFR (eGFR) of >33 mL/min/1.73 m(2) exhibited the fastest illness progression in the study population (-3.655 mL/min/1.73 m(2)), followed by patients with a baseline eGFR of <33 mL/min/1.73 m(2) and a baseline serum phosphorus of >4.3 mg/dL (-2.833 mL/min/1.73 m(2)). Among patients without proteinuria, those aged <67 years exhibited a significantly faster progression, which was even faster for the subgroup with diabetes. Among patients aged >67 years, females had on average a stable eGFR over time, with a large variability. CONCLUSIONS It is possible to rely on a few variables typically accessible in routine clinical practice to stratify patients with a different CKD progression rate. Stratification can be used to guide decisions about the follow-up schedule, treatments to slow progression of kidney disease, prevent its complications and to begin planning for dialysis and transplantation.

Low-Dosage Ibopamine Treatment in Progressive Renal Failure: A Long-Term Multicentre Trial

A multicentre trial (11 nephrology centres) was carried out to test the effects of ibopamine, an orally active dopamine-like drug, on the progression of chronic renal failure. For a 2-year period 189 chronic renal failure patients (serum creatinine level 1.5-4.0 mg/dl) were observed. They were homogeneous for basic nephropathy, degree of residual renal function, blood pressure, and proteinuria. The patients were randomly divided into two groups: 96 took ibopamine at a dosage of 100 mg/day (group A) and 93 served as controls (group B). All were on a low-protein diet (mean 0.8 g/kg body weight). By the end of the observation period, the rate of decrease of the renal function indexes in time proved significantly slower (1.8 times) in group A than in group B. The survival curves for renal function (pre-established end points were creatinine level increases equal to or > 20% and equal to or > 40% of the basal values) proved significantly better (p < 0.02 and p < 0.002 respectively) in group A than in group B. The mean plasma creatinine values rose by 17% in group A and by 36% in group B. The creatinine clearance decreased by 5% in treated patients and by 14% in the controls. Statistical analysis ruled out any possible centre effect. The trial suggests that low-dosage ibopamine administration may be used as a valid and safe pharmacological adjunct for retarding the progression of renal failure in patients with mild or moderate chronic renal impairment.

Post-Dilution Hemodiafiltration With a Heparin-Grafted Polyacrylonitrile Membrane

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post‐dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty‐four patients from eight centers were included in the study and treated by means of post‐dilution on‐line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000‐unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low‐molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post‐dilution hemodiafiltration with reduced doses of LMWH.

Incidence of Cancer in Kidney Transplantation Waiting List Patients: A Single Center Experience

INTRODUCTION It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. MATERIALS AND METHODS We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). RESULTS Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. CONCLUSION The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Native Kidney Function After Renal Transplantation Combined With Other Solid Organs in Preemptive Patients

Kidney transplantations combined with other solid organs are progressively increasing in number. There are no guidelines regarding the nephrologic indications for combined transplantations, namely liver-kidney (LKT), or heart-kidney (HKT), in preemptive patients with chronic kidney failure who are not on regular dialysis therapy. The objective of this study was to assess the functional contribution of the native kidneys after preemptive kidney transplantation combined with other solid organs. From 2004, 9 patients (aged 50.3 +/- 8.5 years) with chronic kidney failure (creatinine 2.5 +/- 1.0 mg/dL) caused by polycystic kidney disease (n = 4), vascular nephropathy (n = 2), interstitial nephropathy (n = 1), glomerulonephritis (n = 1), or end-stage kidney disease (n = 1), underwent combined transplantations (8 LKT, 1 HKT). A scintigraphic functional study (Tc-99DMSA or Tc-99mMAG3), was performed at 4 +/- 3 months after transplantation to evaluate the functional contribution of both the native kidneys and the graft. All patients were given immunosuppressive drugs, including a calcineurin inhibitor (tacrolimus/or cyclosporine). At the time of scintigraphy, renal function in all patients was 1.3 +/- 0.3 mg/dL. The functional contribution of the transplanted kidneys was on average 77 +/- 18%. Only in 1 patient was the contribution of the graft <50%. At follow-up after 36 months, patient and kidney survivals were 100%. The study confirmed a high risk of loss of native kidney function in the presence of organic nephropathy. In light of our experience, a creatinine clearance <30 mL/min in an appropriate cutoff for a combined transplantation. Close clinical and instrumental assessment pretransplant is essential before proceeding with a combined transplant program to exclude functional forms and to optimize the use of organs.

Severe gastrointestinal bleeding in a uremic patient treated with estrogen-progesterone therapy.

Gastrointestinal bleeding is a frequent complication in hemodialysis patients; angiodysplasia is a potential cause, with a higher incidence in uremic patients. We describe a case of severe anemia (Hemoglobin up to 3.5 g/dl) secondary to diffuse angiodysplastic lesions in a hemodialysis patient with mixed connective tissue disease. The case is characterised both by the severity of the clinical picture (extension and entity of angiodysplastic lesions, frequency of bleeding episodes) and by the patients religious faith which made her reject blood transfusions. We underline the efficacy of estrogen-progesterone therapy in view of the modest results obtained with other therapeutic strategies on bleeding.

Donor-Specific Anti-HLA Antibodies After Bone-Graft Transplantation. Impact on a Subsequent Renal Transplantation: A Case Report

Immunological evaluation by panel-reactive antibody (PRA) and determination of anti-HLA specificity are important phases in the evaluation of patients awaiting kidney transplantation. The main causes of immunization are previous solid organ transplantation, hemotransfusion, and pregnancy. It is also possible that immunogenicity can be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone prostheses is not yet understood. A 19-year-old patient with osteosarcoma had undergone resection of the left proximal tibia with reconstruction using human bone in 1997. The donor HLA typing was as follows: A3, A29 (19); B44 (12), Bw4; DR13 (6), DR7, DR52, DR53. The patient was subsequently enrolled onto the waiting list for cadaveric donor kidney transplantation due to chronic kidney failure caused by cisplatin toxicity. Pretransplantation immunological screening using the complement-dependent cytotoxicity (CDC) technique revealed a PRA of 63%. IgG antibody specificities were detected against class I and class II donor antigens, specifically anti-A3, B44, DR7 antibodies, using flow cytometry (Tepnel Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I degrees -II degrees , Tepnel-Luminex) showed direct antibodies against all donor antigen specificities. This case showed immune induction after the implantation of bone prosthesis in a kidney transplant candidate, underlining the importance of the availability of HLA typing data of donors of a human prosthesis.