[Living donor kidney transplant: the crossover modality]. / Il trapianto di rene da donatore vivente: la modalita' crossover.

Living donor kidney transplantation (LKD) has to be considered the best transplant choice for ESRD patients in terms of organ quality and survival. ABO incompatibility and positive cross-match frequently impede LKD. Recently, options based on stronger immunosuppression, apheresis techniques and Ig administration have been proposed to overcome the biological barriers. International guidelines on LKD advise paired exchange as the preferable transplant option to avoid the hazard of blood type or cross-match incompatibility. Since 1986 many paired exchange LKD programs have been started in the world including the USA, Japan, South Korea and, in Europe, the Netherlands, Switzerland, Romania, Germany and Italy. The first Italian paired exchange LKD was performed at the Pisa Transplant Center in November 2005 between three couples of spouses. One year later a National Program was established by the Italian National Transplant Center. The second experience in Italy was again in Pisa in December 2007 between two couples of spouses. International reports have shown that paired exchange LKD offers good clinical results comparable to direct LKD. In our experience paired exchange LKD is to be considered a quality choice for uremic patients, in that it allows them to obtain the benefit of an LKD that would otherwise not be practicable.

Living kidney transplantation: evaluation of renal function and morphology of potential donors.

The evaluation of potential living kidney donors requires an accurate study of renal function and morphology. The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). However, GFR is often estimated from serum creatinine (SCr), cystatin C (SCys), or creatinine clearance (CCr). Otherwise, GFR is predicted using formulas based on SCr or SCys. Ultrasound scanning evaluates morphology and dimensions, while scintigraphy provides information on morphofunctional symmetry of kidneys. The aim of this study in 79 potential donors was to assess the accuracy of the tests employed to estimate GFR and the utility of renal ultrasound and scintigraphy for morphofunctional evaluation of potential donors. GFR (clearance of (99m)Tc-DTPA) was compared with estimates obtained with Cockcroft and Gault (CG-CCr) and Modification of Diet in Renal Disease (MDRD-GFR) formulas, and from SCys (Cys-GFR). The correlation with GFR was statistically significant for SCys and for all estimates, but not for SCr. CCr showed a poor agreement with GFR, with a large range of agreement and a marked and significant overestimation of GFR (33.8 mL/min). The accuracy of CG-CCr and MDRD-GFR as indicators of a GFR < 80 mL/min was better than that of Cys-GFR and CCr. However, their mean prediction errors versus GFR were relevant. Renal dimensions, particularly renal volume, showed a good correlation with GFR. The correlation was higher than that of all prediction equations. The direct measurement of GFR remains the reference method to assess renal function in potential kidney donors. The measurement of renal dimensions can provide useful information also on renal function.

Kidney dimensions at sonography are correlated with glomerular filtration rate in renal transplant recipients and in kidney donors.

The gold standard to assess renal function is the measurement of glomerular filtration rate (GFR). For practical reasons, renal function is often evaluated from serum creatinine (S Cr) or cystatin C (S Cys), and GFR is predicted from SCr. Ultrasound scanning of the kidneys is used only to evaluate renal morphology. The aim of this study was to evaluate the relationship between sonographic renal dimensions and GFR in renal transplant recipients and in kidney donors. GFR (urinary clearance of (99m)Tc-DTPA), S Cr, and S Cys were measured in 33 donors (28 females [F], 5 males [M]; SCr, 0.81-1.90 mg/dL) and 30 recipients (8 F, 22 M; SCr, 0.96-2.42 mg/dL). GFR was also predicted using the Cockcroft and Gault (CG) formula and with the simplified Modification of Diet in Renal Disease (MDRD) formula. Length, width, and depth of kidneys and renal sinus were measured using renal sonography. Among sonographic measurements, kidney length showed the best correlation with GFR. A closer correlation with GFR was found in donors (r = 0.639; P < .00007) than in recipients (r = 0.511; P < .005). In either case, the correlation of kidney length with GFR was greater than that of S Cr or S Cys, and similar to that of CG or MDRD GFR. Accuracy of kidney length as an indicator of GFR impairment was not statistically different from laboratory tests. Only in donors did CG show better accuracy. In conclusion, renal dimensions at sonography closely correlated with GFR. Thus, renal sonography can give information also on the function of the renal graft and of the remaining kidney of living donors.

Neoral versus prograf in simultaneous pancreas-kidney transplantation with portal venous drainage: three-year results of a single-center, open-label, prospective, randomized pilot study.

BACKGROUND: The preferential use of tacrolimus (Prograf) over cyclosporine microemulsion (Neoral) in simultaneous pancreas-kidney transplantation (SPKTx) is mainly based on historical, retrospective studies. We herein report the 3-year results of a single-center, prospective, randomized comparison of the two calcineurin inhibitors in the setting of mycophenolate mofetil (MMF)-based immunosuppression and portal drainage of pancreas allografts. METHODS: Between May 2001 and August 2004, 47 SPKTx recipients who were stratified by recipient sex, were alternatively assigned to treatment with Neoral (n = 22) or Prograf (n = 25). Concurrent immunosuppression included induction treatment with basiliximab and maintenance with MMF and steroids. RESULTS: After a median follow-up of 24.0 months, all patients remained in the study arm into which they were initially enrolled. No pancreas rejection episode was observed. One acute kidney rejection was recorded in the Neoral arm (4.5%) as compared with 7 (28.0%) including one steroid-resistant episode, in the Prograf arm (P = .03). The cumulative incidence of adverse events was 31.8% (n = 7) in the Neoral arm compared with 92.0% (n = 23) in the Prograf arm (P < .0001). One patient died in each study arm. Patient, pancreas, and kidney survivals overlapped at 1- and 3-years posttransplant, namely all 95.4% for the Neoral arm compared with 95.8%, 91.8%, and 95.8%, respectively, for the Prograf arm (P > .05). CONCLUSIONS: We conclude that in MMF-based immunosuppression there is no convincing evidence that Prograf should be preferred to Neoral in SPKTx.

Kidney transplantation from donors aged 65 years or more as single or dual grafts.

AIM: The organ shortage and aging donor population force transplant centers to accept donors previously considered unusable for kidney transplantation. We report the experience of two Italian transplant centers with single (SKTx) and dual (DKTx) kidney transplantation from donors aged 65 years or more. METHODS: The study population comprised 75 SKTx (mean donor age 70.5 years) and 28 DKTx (mean donor age 75.0 years). Kidneys from donors with a calculated admission creatinine clearance <50 mL/min, a Karpinski's score on kidney biopsy between 5 and 7, or both were allocated to DKTx. Grafts with better function or lower biopsy scores were employed for SKTx. RESULTS: Delayed graft function occurred in 45.3% of SKTx and in 39.3% of DKTx. After a mean follow-up period of 30.0 +/- 19.5 months, the acute rejection rate was 24.0% in SKTx and 7.1% in DKTx. Mean serum creatinine was 1.8 +/- 0.9 and 1.8 +/- 1.3 mg/dL in SKTx, and 1.8 +/- 1.6 mg/dL and 1.3 +/- 0.2 mg/dL in DKTx at 1 and 5 years, respectively. Patient survival was 93.3% and 91.2% in SKTx, and 92.9% and 92.9% in DKTx at 1 and 5 years, respectively. Graft survival was 92.0% and 88.3% in SKTx, and 89.3% and 89.3% in DKTx at the same time intervals. Keeping preservation time below 16 hours and avoiding calcineurin inhibitors were both associated with improved graft survival and function. CONCLUSION: Careful donor selection, short preservation time, and tailored immunosuppression allow safe and efficient use of elderly donor kidneys.

Kidney transplantation from donors aged more than 65 years.

BACKGROUND: There are no agreed criteria to predict the outcome of elderly donor kidneys or to decide between single (SKG) or dual (DKG) kidney graft transplantation. METHODS: Between January 1999 and January 2003, 46 SKG and 14 DKG were performed from elderly donors (mean donor age 71.6 years; range: 66 to 87). Kidney biopsies were scored according to Karpinski. A calculated admission creatinine clearance <50 mL/min and/or a biopsy score of 5 or 6 were used to select kidneys for DKG. Grafts with better function or lower biopsy scores were employed for SKG. RESULTS: Mean cold ischemia time (CIT) was 16.8 hours (range 8.1 to 28.6) in SKG, and 16.3 hours (range 4.6 to 24.3) for the first kidney and 17.4 hours (range 5.1 to 25.9) for the second graft in DKG. Delayed graft function (DGF) occurred in 34.1% SKG and in 28.5% DKG. Acute rejection rates were 9.1% for SKG and 0% for DKG. Three-year actuarial patient survival rates were 97.7% for SKG and 92.9% for DKG; for kidneys, 95.4% and 92.9%. One-year mean serum creatinine levels were 1.8 mg/dL (range 1.1 to 4.0) for SKG and 1.2 mg/dL (range 1.0 to 1.8) for DKG (P =.01). CIT longer than 16 hours was related to increased rates of DGF for both SKG (45.4% vs 22.7%) or DKG (42.9% vs 14.3%) and reduced 3-year graft survival rates (SKG: 90.9% vs 100%; DKG: 85.7% vs 100%). CONCLUSIONS: With stringent selection criteria and short CIT (<16 hours), elderly donor kidneys may show good results, thus meaningfully expanding the donor pool.

Solitary pancreas transplantation: preliminary findings about early reduction of proteinuria in incipient or evident diabetic type I nephropathy.

OBJECTIVE: Our work was aimed to evaluate the precocious reduction of proteinuria in patients suffering from diabetes mellitus type 1 with incipient and evident nephropathy after isolated pancreas transplantation (PTA). MATERIALS AND METHODS: From December 2000 to March 2003, we followed 24 PTA grafts in 24 patients with diabetes mellitus type 1 (mean age 37.8 years; mean duration of diabetes 24.8 years). The pancreas was transplanted with portal-enteric drainage in 23 patients and systemic-enteric in 1 patient. The immunosuppressive therapy used basilixmab induction and tacrolimus, mycophenolate mophetil (MMF), and low dose steroid maintenance therapy. The renal function, proteinuria, and the glucose metabolic parameters were evaluated before and during the following months after transplant. RESULTS: All patients are alive and twenty-one have a well-functioning pancreas with three grafts lost. All patients had persistence of normal renal function. Before transplantation 12 patients displayed proteinuria that was clearly reduced in 11 and gone in three patients, all of whom were insulin-independent. CONCLUSIONS: TPA seems to reduce, and in some cases to regress, the proteinuria associated with early diabetic nephropathy.

Dissociation between carotid artery lesions and lipid parameters in recipients of successful kidney graft.

BACKGROUND: The relationships between lipid levels and atherosclerotic lesions of carotid arteries in kidney graft recipients are still unclear. METHODS: We evaluated carotid morphology in 53 recipients of functioning renal transplantation, and studied the relationship of carotid artery wall lesions with relevant clinical and laboratory risk factors for cardiovascular disease. The patients were on stable, cyclosporine-based immunosuppressive therapy. RESULTS: The main clinical characteristics of patients were: age, 46.5 +/- 10.1 years; males/females, 40/13; body mass index, 25.8 +/- 4.4 kg/m2; duration of transplantation, 43 +/- 52 months. Ultrasonographic scanning of carotid arteries showed the presence of lesions (intimal-media thickness and/or plaque) in 28 patients (52.8%). These recipients differed from patients without carotid lesions in terms of age (50.4 +/- 9.0 vs 42.2 +/- 9.7 years, p < 0.01) and duration of pre-transplant dialysis (4.6 +/- 3.4 vs 2.3 +/- 1.9 years, p < 0.01), whereas no statistically significant difference was observed as for total cholesterol (230 +/- 44 vs 235 +/- 35 mg/dl), LDL-cholesterol (142 +/- 32 vs 143 +/- 30 mg/dl), HDL-cholesterol (52 +/- 12 vs 58 +/- 20 mg/dl) and triglycerides (178 +/- 94 vs 167 +/- 89 mg/dl). The percentage of post-transplant diabetes was 3-fold higher in patients with carotid lesions (25 vs 8%). No difference was observed as for the following parameters: body mass index, duration of transplantation, fibrinogen levels, DDimer concentrations, reactive C-protein values, prevalence of hypertension, percentage of smokers vs non-smokers. CONCLUSIONS: The present study supports the view that carotid artery lesions in kidney graft recipients on stable, cyclosporine-based immunosuppressive therapy may not be related to circulating lipid values.

Low-antigen-content diet in the treatment of patients with IgA nephropathy.

Since dietary macromolecular antigens can be involved in the pathogenesis of IgA nephropathy (IgAN), the effect of a low-antigen-content diet was evaluated in 21 patients (10 women, 11 men, mean age 27.7 +/- 10 years) with immunohistochemical findings of active IgAN. The diet was followed for a 14-24-week period (mean 18.8 +/- 6); in all cases the effects of the treatment were evaluated by clinical and serological parameters, and in 11 patients also by repeat renal biopsy. After dietetic therapy a significant reduction of urinary proteins was recorded (P < 0.001); in particular, heavy proteinuria (> 1 g/day), present in 12 cases during the 6 months preceding the treatment, was markedly reduced or disappeared in 11. At post-treatment control biopsy mesangial and parietal deposits of immunoglobulins, complement C5 fraction and fibrinogen were significantly reduced. The improvement of the objective parameters such as heavy proteinuria, a strong predictor of a poor prognosis, and of immunohistochemical alterations indicate that a low-antigen diet can positively affect patients with IgAN. These results could be ascribed to a reduction of nephritogenic food antigen input and to a putative functional restoration of the mononuclear phagocytic system.

Treatment of the renal involvement in mixed cryoglobulinemia with prolonged plasma exchange.

Nine patients with mixed cryoglobulinemia and severe membranoproliferative glomerulonephritis were treated with plasma exchange alone or in combination with medium to low amounts of corticosteroids, but never with cytotoxic drugs. In 5 patients renal function and/or proteinuria improved after plasma exchange, and no clinical relapse usually occurred when the procedures were reduced or discontinued. These procedures seemed of particular effect in the presence of histologically active and not irreversible lesions and rapid deterioration of renal function. While cryocrit almost invariably decreased, circulating immune complex or complement levels were unpredictably affected by plasma exchange. Cryocrit, but not immune complex or complement levels, was the serological parameter which most often closely correlated with signs of renal involvement (i.e., proteinuria and/or serum creatinine). Thus, plasma exchange might be a safe and useful tool in the treatment of an often drug-resistant and rapidly progressive renal involvement occurring in patients with mixed cryoglobulinemia.

Prolonged plasma exchange in the treatment of renal involvement in essential mixed cryoglobulinemia.

Four men and 2 women with Essential Mixed Cryoglobulinemia and a membrano-proliferative glomerulonephritis were treated with prolonged Plasma Exchange without the addition of cytotoxic agents. All patients had Nephrotic Syndrome and Renal Insufficiency. Three of them presented a rapid deterioration of renal function just prior to Plasma Exchange treatment. Total number of procedures varied for each patients from 24 to 105. Serum creatinine decreased significantly in those patients with rapid deterioration of renal function, while it was not modified in the 3 with stable chronic renal failure. In no instance major side effects were recorded, and relapses of the disease did not occur, after gradually tapering of Plasma Exchange sessions. These data suggest that Plasma Exchange alone, if early instituted, may be an effective and safe treatment of Essential Mixed Cryoglobulinemia Glomerulonephritis.