Biomedical subjects

Graziella Zacchello

Publications and source records attributed to Graziella Zacchello.

At least 19 recordsLinked to original sources

PubMed2006

Cadaver kidney transplantation and vascular anomalies: a pediatric experience.

BACKGROUND: The incidence of donor kidneys with vascular anomalies ranges from 18% to 30%; such kidneys are usually at increased risk of vascular and urological complications. The aim of this study was to determine whether the use of cadaver kidneys with vascular anomalies would adversely affect posttransplant graft and patient outcome. METHODS: From October 1987 to January 2004, 241 patients underwent kidney transplantation in our pediatric surgery department. Vascular anomalies were noted in 77/241 grafts (31.9%); 50 (64.9%) had multiple renal arteries and 22 (28.5%) venous anomalies. Patients were divided into three groups: Group A (1 renal artery and vein, 1 arterial and venous anastomosis [n = 161]), Group B (> 1 renal artery or vein, 1 arterial and venous anastomosis [n = 33]), and Group C (> 1 renal artery or vein, > 1 arterial and venous anastomosis [n = 47]). We compared the three groups for: patient and graft survival, incidence of posttransplant acute tubular necrosis, vascular and urological complications, postoperative mean creatinine levels, and posttransplantation hypertension. RESULTS: We found no significant differences among the three groups regarding episodes of acute rejection or acute tubular necrosis. Creatinine levels reached normal levels within 30 days in all the groups without any significant differences. Furthermore, patient and graft survival were excellent (100% and 97%). CONCLUSIONS: The presence of vascular anomalies and their multiple or complex repair does not represent a theoretical disadvantage even in pediatric patients. In order to maximize the quantity and quality of donor kidneys especially in pediatric population, kidneys with vascular anomalies may be implanted with very little risk.

Adolescent↗

PubMed2006

A prospective multicentre study of the nutritional status in children on chronic peritoneal dialysis.

The anthropometry-bioimpedance analysis-nutrition (ABN) score is a recently proposed objective method of assessing malnutrition in children on chronic peritoneal dialysis (CPD) that uses nine parameters based on anthropometry, skinfold thickness and bioimpedance analysis. The aim of this prospective, cross-sectional study was to apply it to children treated with CPD in seven Italian paediatric nephrology centres, with a score of < 10.33 (the 3rd percentile in a population of 264 healthy children) classifying the children as malnourished. The other considered parameters were age, age at the start of dialysis and duration of dialysis; serum haemoglobin, urea, creatinine, total protein, albumin, transferrin, bicarbonate and C-reactive protein; residual urine output; urinary and peritoneal creatinine clearance; and daily protein and energy intake. The study enrolled 43 patients (mean age 10.2 +/- 4.2 years), 21 of whom (48.8%) had an ABN score of < 10.33: 15 with mild, five with moderate, and one with severe malnutrition. The malnourished patients started CPD at a younger age (P < 0.05) and had a longer duration of dialysis (P < 0.01), and a significant worsening in nutritional status was observed in those treated for more than 12 months of dialysis; they also had significantly lower serum albumin, creatinine and haemoglobin levels. In conclusion, protein-calorie malnutrition is common in children receiving CPD. A younger age at the start of dialysis and a longer duration of treatment are clear risk factors, and counterbalance the long-term viability of CPD in paediatric age.

Adolescent↗

PubMed2006

The pharmacokinetics and immunosuppressive response of tacrolimus in paediatric renal transplant recipients.

The aims of our trial were to study the pharmacokinetics of tacrolimus in paediatric kidney transplant recipients. The study comprised 25 patients (median age 13 years, range 2-20 years) followed for 12 months; five pharmacokinetics profiles (within the first and second week and after 1 month, 6 months and 12 months) were obtained. Patients were divided into two groups: six children<6 years old and 19 older children. Tacrolimus was given at an initial dose of 0.15 mg/kg twice a day. Blood samples were drawn before and 1 h, 2 h, 3 h, 4 h, 6 h, 9 h and 12 h after drug administration. Patient and kidney survival rates were 100% at 1 year. At 6 months and 12 months creatinine clearance was 68.5+/-16.3 ml/min per 1.73 m2 and 64.0+/-15.2 ml/min per 1.73 m2 body surface area, respectively. Tacrolimus trough levels were 7.8+/-1.9 ng/ml and 7.3+/-2.5 ng/ml. The area under the concentration-time curve for 0 h to 12 h (AUC0-12) normalised to a dose of 0.15 mg/kg, increased with time from the kidney transplantation and stabilised after the 6th month post-transplantation. During the first month after transplantation the normalised tacrolimus concentration-time profiles were significantly greater in the older children (P<0.05); the actual doses were significantly greater in the younger children (P<0.05). In conclusion, initial doses of 0.15 mg/kg twice a day orally are safe and guarantee a satisfactory degree of immunosuppression, with our therapeutic regimen. Children<6 years old need to start with a 50% higher tacrolimus dose to achieve the same pharmacokinetic and immunosuppressive results.

Adolescent↗

PubMed2006

Oxidative stress and post-transplant hypertension in pediatric kidney-transplanted patients.

OBJECTIVE: To test the hypothesis that oxidative stress signaling contributes to post-transplant endothelial dysfunction and hypertension in pediatric post-transplant hypertension. STUDY DESIGN: This study evaluated in 16 pediatric renal transplant patients, divided in two groups based on the presence of post-transplant hypertension, the oxidative stress status measuring the gene expression (reverse transcription-polymerase chain reaction) of two major oxidative stress-related proteins, p22(phox) and heme oxygenase-1 (HO-1). Total plasma antioxidant power (ELISA) was also evaluated. RESULTS: Mononuclear cell p22(phox) gene expression was higher in hypertensive patients compared with the normotensive group (0.91 +/- 0.06 vs 0.79 +/- 0.08 densitometric units, P < .02), whereas HO-1 RNA production and total plasma antioxidant power were higher in the normotensive group (0.38 +/- 0.04 vs 0.20 +/- 0.11 d.u., P < .006, and 1189.35 +/- 145.75 vs 772.71 +/- 196.03 micromol/L, P < .01, respectively). CONCLUSIONS: Oxidative stress is associated with post-transplant hypertension in hypertensive pediatric kidney-transplant patients, who therefore are at risk of oxidative stress-induced organ damage. They might benefit from treatments addressing not only hypertension but also oxidant-related complications.

Adolescent↗

PubMed2005

Kidney transplantation into bladder augmentation or urinary diversion: long-term results.

BACKGROUND: We report on a single-institutional experience with renal transplantation in patients with severe lower urinary tract dysfunction (LUTD) who underwent bladder augmentation or urinary diversion, and assess the long-term results. METHODS: From September 1987 to January 2005, 255 patients (161 male and 94 female), 7 months to 39 years old of age (median age at time of transplantation 14 years), received 271 kidney transplants. Etiology of end-stage renal disease was LUTD in 83 cases. Among these patients, 24 had undergone bladder augmentation or urinary diversion. RESULTS: We identified two groups of patients surgically treated due to LUTD: group 1 included 16 patients (eight male, eight female) aged 4 to 39 years (median 19 years) with bladder augmentation, whereas in group 2, seven patients (five male, two female) 7 months to 31 years old (median 17 years) with incontinent urinary diversion were reported. In the first group, surgical complications after kidney transplantation included one urinary fistula, one ureteral stenosis. Three patients of second group developed recurrent urinary tract infection. Cumulative graft survival rates of all patients transplanted was 69.4% after 15 years, whereas in the two investigated groups, group 1 and group 2, was 80.7% and 55.5% respectively (P=NS.). CONCLUSIONS: Drainage of transplanted kidneys into an augmented bladder or urinary diversion is an appropriate management strategy when the native bladder is unsuitable. Kidney transplantation in patients with bladder augmentation or urinary diversion for LUTD let achieve similar results to those obtained in the general population with normal lower urinary tracts.

Adolescent↗

PubMed2005

Pharmacokinetic of cyclosporine microemulsion in pediatric kidney recipients receiving A quadruple immunosuppressive regimen: the value of C2 blood levels.

BACKGROUND: The management of cyclosporine therapy in pediatric kidney-transplant recipients is largely based on single center's experience rather than on a univocal pharmacokinetic approach based on therapeutic drug monitoring. A prospective multicenter trial was designed to address the question whether C2 blood level monitoring of cyclosporine microemulsion therapy is feasible in the pediatric setting. METHODS: Sixty-four pediatric kidney-transplant recipients receiving a triple immunosuppressive regimen based on cyclosporine microemulsion had their cyclosporine dose adjusted to the same protocol-defined C2 targets from the time of the transplant until 2 years posttransplant. The interim analyses after 1 year of enrollment is presented in this study. RESULTS: One-year patient and graft survival were 100% and 94.8%, respectively. One-year rejection rate was 15%. C2 management of cyclosporine did not affect graft function: 1-year serum creatinine and glomerular filtration rate were 1.3+/-1 mg/mL and 71.2+/-20 mL/min/1.73 m2, respectively. C2 was the best single-point predictor of the area under the concentration curve throughout the entire follow-up, with a mean coefficient of correlation of 0.97+/-0.01. CONCLUSIONS: C2 management of cyclosporine microemulsion therapy is effective and safe in pediatric kidney-transplant recipients given a combined immunosuppressive treatment.

Adolescent↗

PubMed2005

One-year results of basiliximab induction and tacrolimus associated with sequential steroid and MMF treatment in pediatric kidney transplant recipient.

We report the 1-year results with a triple immunosuppressive regimen in pediatric recipients of a first kidney transplant, in order to evaluate its safety and efficacy in the prevention of acute rejection and in the reduction of steroid side effects. The immunosuppression is as follows: (i) basiliximab (20 mg if body weight >30 kg; 10 mg if < 30 kg) is given pretransplant and at day 4; (ii) tacrolimus (Tac) is administered in order to obtain blood trough levels of 10-20 and 5-10 ng/ml during and after the first 2 months post-transplant, respectively; (iii) steroids are tapered during the first 6 months and then replaced by mycophenolate mofetil (depending on previous rejection episodes, infection status and the result of a routine biopsy) at a dosage of 4-600 mg/m(2) body surface area. Fifty-three children (median age 13 years, range 2-20) have entered this protocol. One-year patient and kidney survival are 100% and 94% respectively. During the first year a total of nine rejections in seven patients (13% of the cohort study) occurred, all but one responsive to steroids. Renal function was satisfactory throughout the first year (mean CrCl was 63.8 +/- 18 and 60.9 +/- 15.5 ml/min/1.73 m(2) at 6 and 12 months respectively). Subclinical signs of rejection were absent in more than 80% of biopsies (grade I Banff) at 6 months (n = 47); at the 12th month biopsy (n = 42) score I was stable in 20 patients (16 after stopping steroids) and had worsened in eight biopsies (six after stopping steroids). Major complications were insulin-dependent diabetes in three (5.6%) children with the need of insulin for a mean of 3 months; transient hyperglycemia (11 patients), treated with a dietary regimen, symptomatic viral infections (in 11 patients: two parvovirus B19, three cytomegalovirus and two Epstein-Barr virus systemic infections, three interstitial pneumonia, two BK nephritis). Tac doses more than 0.3-0.4 mg/kg/day are at significantly higher risk of viral infection. In conclusion, this immunosuppressive regimen is associated with a low percentage of clinical (13%) and subclinical rejections, but with a relatively high number of infections, prevented by a reduction in Tac doses (<0.3 mg/kg/day) during the first 2 months after transplantation. The assessment of steroid withdrawal needs a longer follow-up.

Adolescent↗

PubMed2005

Skin disorders in patients transplanted in childhood.

Only few data are available on skin disorders in pediatric organ transplant recipients. In order to describe the whole range of dermatological diseases in a population of pediatric organ transplant recipients, we studied a group of 217 consecutive organ transplant recipients (168 kidney, 29 heart, 19 liver, one lung) aged <18 years at transplantation followed at a single center. A total of 193 patients showed at least one skin disorder; 149 had more than one skin disease. The most common skin infections were warts (24.4%), pityriasis versicolor (20.7%), folliculitis (12.9%), intertrigo (6.5%); the most common drug side effects were hypertrichosis (69.6%), steroid acne (39.6%), gingival hyperplasia (29%) and severe xerosis (20.7%). Two patients (0.9%) developed nonmelanoma skin cancer. Our study summarizes the main skin complications in patients transplanted in childhood and underlines the necessity of regular dermatologic surveillance of these patients.

Adolescent↗

PubMed2005

Renal transplantation. Strategies to prevent organ rejection--the role of an inter-regional reference center.

This paper summarizes the role of the Inter-Regional Reference Center (RC) of the North Italy Transplant program (NITp), in coordinating a donor procurement and organ transplantation network, with a special focus on the strategies to minimize immunological risk and complications after transplantation. In the NITp, patients enrolled on the renal transplantation (RT) waiting list are typed for HLA-A,B,DRB1 antigens with a genomic method. They are periodically screened for the presence of lymphocytotoxic antibodies in their serum by the RC and their suitability to receive the transplant is checked periodically. Cadaver kidney allocation is ruled by a computerized algorithm, named NITK3, established in 1997, which aims at ensuring quality, equity, transparency and traceability during all the phases of the allocation decision-making process. NITK3 has been set up by the NITp Working Group on the basis of biological, medical and administrative criteria and it is periodically reviewed after the analysis of transplant results. In this paper, we show the results of a preliminary analysis of RTs performed from 1998 to 2002 in nine out of sixteen centers of the NITp area, which demonstrates the general quality of the NITp program in terms of patients and graft survival and the special attention to the patients at higher immunological risk.

Adolescent↗

PubMed2004

Renal transplantation in prune-belly syndrome.

We assess the effect of the prune-belly syndrome (PBS) on renal transplantation outcome. Six renal transplantations were performed in five boys affected by PBS (median age 5.8+/-2.1 years, median weight 13.6+/-2.4kg). Renal graft survival, graft function, lower urinary tract dysfunction, urinary tract infections (UTIs), associated complications and patients' survival after 1 and 5 years of follow-up were analysed. The rate for 1-5-year graft survival was 66.7% (mean serum creatinine 98-103 micromol/l). The surgical treatment of the documented bladder obstruction (two patients) and the severe abdominal wall deficit (one patient) led to a reduction of UTI: the patients maintained their native urinary tract and none received prophylactic antibiotics. The lack of abdominal wall musculature led to severe mechanical complication in one patient, but Monfort's abdominal wall reconstruction was able to restore the graft's function. The outcome of patients with PBS who undergo renal transplantation is good. Before the transplant, an accurate assessment of urinary tract anomalies and deficiency of the abdominal wall musculature is mandatory, to program the appropriate treatment and obtain a good long-term prognosis for the renal graft.

Abdominal Wall↗

PubMed2004

Selective decrease in urinary aquaporin 2 and increase in prostaglandin E2 excretion is associated with postobstructive polyuria in human congenital hydronephrosis.

This study was undertaken to determine the role of aquaporin 2 (AQP2) in the impaired urinary concentrating capacity observed in patients who underwent pyeloplasty because of congenital unilateral hydronephrosis as a result of pyeloureteral junction disease. Twelve children (mean age, 8 +/- 2 mo) were examined in the study. From day 1 to day 5 after surgery, the urine was collected separately from pyelostomy draining only from the postobstructed kidney and from the bladder catheter draining mostly from the contralateral kidney used as internal control. After pyeloplasty, the postobstructed kidney was characterized by a reduced urinary excretion of AQP2 (approximately 54%) associated with polyuria that persisted from day 1 to day 5 (433 +/- 58 versus 310 +/- 74 ml/24 h at day 1; 326 +/- 44 versus 227 +/- 26 ml/24 h at day 5). In parallel, urine osmolality from the postobstructed kidney was significantly reduced compared with the contralateral kidney (111 +/- 12 versus 206 +/- 49 at day 1; 136 +/- 24 versus 235 +/- 65 mOsm/kg at day 5). Creatinine clearance from the postobstructed kidney was not significantly different compared with the contralateral kidney throughout the 4 d after surgery. However, on day 5, creatinine clearance from the postobstructed kidney became significantly lower. Prostaglandin E2 in the urine from postobstructed kidneys was found to be twofold higher than in the contralateral samples (26.0 +/- 6.7 versus 13.5 +/- 2.5 at day 5). It is concluded that (1) the selective downregulation of AQP2 in postobstructed kidney may account for the higher excretion of hypotonic urine, and (2) the local increase in prostaglandin E2 synthesis in postobstructed kidney may be involved in AQP2 downregulation and in maintaining a GFR similar to that of the contralateral kidney.

Adolescent↗

PubMed2003

A multicenter experience on patient and technique survival in children on chronic dialysis.

In this study we compared patient and technique survival of 163 new hemodialysis (HD) patients (age 11.4+/-3.1 years) and 295 peritoneal dialysis patients (7.7+/-4.8 years. P< 0.001), treated in 23 dialysis centers participating in the Italian Registry of Pediatric Chronic Peritoneal Dialysis (CPD) during the years 1989-2000. Three HD (1.8%) and 17 CPD (5.8%) patients died; the overall average death rate was 9.8/1,000 patient-years in HD and 29.8/1,000 patient-years in CPD patients. No statistically significant difference in patient survival between CPD and HD was found, while the survival of 102 CPD children younger than 5 years at the start of dialysis was lower ( P=0.0001) than that of 193 CPD and 160 HD patients aged 5-15 years. We registered 12 modality failures among HD (7.4%) patients and 44 among CPD (14.9%) patients. The main causes were vascular access failure and patient choice in HD, and infection in CPD patients. Technique survival was lower ( P=0.007) in CPD than in HD patients; a statistically significant difference ( P=0.01) was also observed between both the 0- to 5- and the 5- to 15-year-old CPD patients and the HD patients aged 5-15 years. Logistic regression analysis confirmed age at initiation of dialysis to be a predictor of patient death ( P=0.0001) in the whole patient population, and of technique failure in HD ( P=0.006) but not in CPD patients ( P=0.16).

Adolescent↗

PubMed2003

Risk factors for poor renal prognosis in children with hemolytic uremic syndrome.

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D(-)STEC(- )recovered normal renal function compared with 65%-76% of D(+)STEC(+), D(+)STEC(-) and D(-)STEC(+ )patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D(-) but STEC(+) patients have a significantly better prognosis.

Adolescent↗

PubMed2003

Urea percentiles in children with chronic renal failure. Data from the ItalKid project.

In chronic renal failure high serum urea levels (sUrea) are correlated with the onset of uremic symptoms. Urea has generally been considered relatively non-toxic, functioning more as a surrogate for other toxic solutes; however, it has been recently reported that it can contribute to uremic toxicity. Clinically sUrea are often difficult to interpret because of the wide range of kidney functions. To obtain a practical and easily accessible tool to evaluate sUrea, we have produced percentile curves for different ranges of chronic renal failure, defined with creatinine clearance ( C(Cr)) obtained with the Schwartz formula. Data were obtained from the Italian Pediatric Registry of Chronic Renal Failure (ItalKid); its inclusion criteria are: (1) C(Cr )<75 ml/min per 1.73 m(2), (2) age <20 years at time of registration, and (3) conservative treatment. To obtain the percentiles, the following patients were excluded: patients with an underlying disease, a concomitant treatment, or a disorder that could affect urea metabolism, per se, and/or food intake, and patients aged <2 years. The study group included 690 subjects (mean age 9.56+/-4.54 years, 485 males). In total, 2,085 observations (C(Cr )and sUrea) were available for the construction of the percentile curves. A median of 258 (range 99-380) observations was obtained for each of the eight different categories of C(Cr )(intervals of 10 ml/min per 1.73 m(2)). The 10th, 25th, 50th, 75th, and 90th percentiles were calculated and a graph was produced. Patients with the highest urea percentiles showed significantly higher plasma levels of phosphorus and parathyroid hormone and significantly lower hemoglobin concentrations and bicarbonate levels. Our percentile curves may help to identify subjects with inappropriate sUrea for a given C(Cr).

Adolescent↗

PubMed2003

Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation.

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.

Acute Disease↗

PubMed2002

Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.

Acute Disease↗

PubMed2002

Middle molecule and small protein removal in children on peritoneal dialysis.

BACKGROUND: Dialysis efficiency has a great influence on the outcome of patients. Few data are available on the removal of solutes with molecular weights higher than urea and creatinine. The aim of our study was to assess the transport and the removal of substances with molecular weights up to 15 kD and to evaluate the contribution of residual renal function in peritoneal dialysis (PD) children. METHODS: Seventeen patients of 12 +/- 4 years undergoing automated PD were studied. Ten patients had 563 +/- 355 mL/day of urine output, and 7 were anuric. During a standardized nightly intermittent PD (NIPD) session, a single-injection inulin clearance was performed. Urea, creatinine, inulin (measured by HPLC), cystatin C and beta2-microglobulin (beta2m) were measured in blood, urine and dialysate. Clearances (L/week/1.73 m2) and weekly solute removal index (SRI) were calculated for all the solutes; weekly Kt/V was calculated for urea. RESULTS: In non-anuric versus anuric patients the total clearances were: urea 82.6 +/- 18.3 versus 71.3 +/- 26.4; creatinine 82.7 +/- 28.6 versus 47.8 +/- 18.8; inulin 42.8 +/- 11.3 versus 32.8 +/- 20.4; beta2m 14.2 +/- 13.8 versus 9.2 +/- 8.3; cystatin C 20.2 +/- 9.4 versus 9.7 +/- 4.8. In the patients with residual diuresis, the urea was removed mainly by PD (69.2%), while inulin, beta2m and cystatin C were removed by renal clearance (64.0%, 79.5% and 62.8%, respectively). Total, peritoneal and renal weekly Kt/V values in the subjects with residual renal function, were 2.86 +/- 0.70, 1.99 +/- 0.40 and 0.87 +/- 0.43, respectively. Peritoneal weekly Kt/V in the anuric patients was 2.36 +/- 0.85; total weekly Kt/V in the total group was 2.65 +/- 0.78. Weekly SRIs in non-anuric versus anuric patients were: urea 2.56 +/- 0.58 versus 2.09 +/- 0.74; creatinine 2.66 +/- 0.73 versus 1.46 +/- 0.56; inulin 2.36 +/- 0.92 versus 1.64 +/- 1.60; beta2m 1.26 +/- 1.10 versus 1.20 +/- 1.90; cystatin C 1.72 +/- 0.83 versus 1.58 +/- 1.62. CONCLUSIONS: Solutes removed during PD tend to decrease following an increase in molecular weight of the substance. Since anuric patients are at higher risk of middle molecule and small protein accumulation, more attention should be paid to the removal of middle molecules. Further studies should be undertaken to evaluate whether removing them has a clinical impact and to determine their threshold levels.

Adolescent↗

PubMed2002

Expression of nuclear transcription factor PAX2 in renal biopsies of juvenile nephronophthisis.

PAX2, a homeotic gene of 'paired box family', is a nuclear transcription factor expressed in mesenchymal/epithelial conversion during the early stages of nephrogenesis; however, its repression is necessary for terminal differentiation of mature tubular cells. Transgenic overexpression in animal model causes epithelial hyperproliferation and microcyst formation. In humans, PAX2 expression has been observed in cystic and dysplasic tubular epithelia in kidney malformation and in kidney disease. We have investigated PAX2 expression and its colocalization with cytokeratin and/or vimentin in 17 biopsies of juvenile nephronophthisis (NPH), an autosomal-recessive renal disease characterized by diffuse renal fibrosis and occasional cysts. Fourteen cases were analyzed for deletion and mutation in the NPH1 gene locus and 33% resulted to be deleted or mutated; for the remaining cases the diagnosis was based on clinical and pathological criteria. The control group included 4 congenital dysplastic kidneys, and 10 biopsies of nephropathies with secondary chronic tubulointerstitial damage. In all cases of renal dysplasia a strong nuclear positivity was observed in immature tubules surrounded by alphaSMA-positive mesenchymal cells. In NI biopsies the tubular epithelia were almost PAX2 negative, although tubulointerstitial damage was severe. In 14/17 NPH1 moderate-to-strong nuclear PAX2 positivity of tubular cells was observed, particularly in cystic distal tubules located at the corticomedullary junction, but also in proximal tubular sections. The PAX2 signal co-localized more with cytokeratin staining than with vimentin. Our results confirm the observation of PAX2 expression in immature dysplastic tubules and its repression in mature renal tubular cells, also in the presence of severe secondary interstitial fibrosis. PAX2 seems to be overexpressed in NPH. The genetic defect of NPH, a disease probably due to a primary defect along the cascade of mesenchymal epithelial differentiation, could generate a functionally abnormal protein involved in focal adhesion signaling and cell/matrix interaction. The failure of PAX2 repression or its reactivation in NPH could be a marker of hyperproliferation and incomplete maturation of epithelial tubular cells, probably due to a defect cell/matrix cross-talk, and involved in interstitial fibrosis and cysts formation.

Biopsy↗