Malekzadeh Mh

Progression to end-stage renal disease in children with obstructive uropathy.

The course of 54 patients (35 boys and 19 girls) with end-stage renal disease resulting from obstructive uropathy was reviewed. The mean age at the initial sign of obstructive uropathy was 3.5 years. Twenty-two patients (41%) manifested evidence of obstructive uropathy during the first year of life. The mean age at the time of onset of ESRD (dialysis) was 12.2 years and was similar in boys and girls. The mean time interval between the first sign of obstructive uropathy and the initiation of dialysis was nine years. Fourteen patients operated upon at less than one year of age developed ESRD one to 20 years (mean ten years) following their initial surgery. Progression to ESRD occurred despite appropriate surgical management, including corrective as well as diversionary urologic procedures. However, because the patients were selectively referred for care of ESRD, no assessment of the incidence of ESRD caused by obstructive uropathy was possible. The data indicate that prolonged follow-up periods are necessary to assess the ultimate outcome of renal function in young patients with obstructive uropathy. Despite early intervention and intact renal function for many years during childhood, progression to ESRD may occur.

SUCCESSFUL RENAL ALLOGRAFTS ACROSS A POSITIVE CROSS-MATCH FOR DONOR B-LYMPHOCYTE ALLOANTIGENS

Seven patients received a renal allograft with negative standard and T-lymphocyte microlymphocytotoxicity cross-matches, but a positive B-lymphocyte cross-match using donor lymphocytes. In spite of this presensitisation, none underwent hyperacute rejection and all are functioning from one and a half to six months after transplantation. This procedure may help in the detection of false-positive cross-matches and possibly in detection of enhancing antibodies against a specific donor.

Renal Transplantation in Children with Obstructive Uropathy

The outcome of renal transplantation was examined in 52 pediatric patients (mean age 13 years) whose primary renal disease was obstructive uropathy. The bladder was used at transplantation in 45 allograft recipients, 39 of whom had had a previous lower urinary tract operation or bladder defunctionalization. An ileal loop was used in 7 recipients. The 52 patients received 73 renal allografts from 58 cadaver and 15 live-related donors. Presently, 40 patients (77 per cent) have functioning allografts, 4 have returned to dialysis and 8 (15 per cent) have died. The results indicate that the outcome of renal transplantation in patients with obstructive uropathy is similar to that of other transplant recipients. Damaged and defunctionalized bladders may be used successfully in most cases. If necessary an ileal conduit is an effective alternative. Post-transplant urologic complications occur with increased frequency but with appropriate management allograft salvage and patient survival are excellent.

Renal transplantation in children less than 5 years of age.

19 young children (less than 5 years old) have received 31 renal transplants from 4 live relatives and 27 cadaver donors. The 2-year allograft survival rate for the patients receiving their 1st allograft from the 4 live donors was 75 +/- 22% while for the patients receiving their 1st allograft from 15 cadaver donors was 26 +/- 11%. 10 children are currently surviving with functioning allographs (7 cadavers and 3 live relatives); 4 have died and 5 are undergoing dialysis after the loss of at least one allograft. Despite the poor allograft survival rate the fact that 7 children are surviving with cadaver allografts indicates that the lack of a living related donor should not prevent transplants in young children.

Anti-B Lymphocytotoxins in Renal-Allograft Rejection

To determine the possible role of the B lymphocyte alloantigen system in renal-transplant rejection, we examined serum specimens from 81 allograft recipients for cytotoxic activity against a panel of normal B lymphocytes. Specimens from 22 of 25 recipients undergoing allograft rejection demonstrated strong B-lymphocyte cytotoxicity whereas only 13 of 56 recipients with normal allograft function showed similar B lymphocyte cytotoxocitiy (P less than 0.0001). In the serum samples of recipients with graft rejection who were followed sequentially, B-lymphocyte cytotoxicity preceded or was concurrent with the onset of functional impairment. The results show that anti-B-lymphocyte antibodies are associated with rejection, but it is quite possible that they are the products of rejection rather than the cause.

Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation.

Gonzalez E, Ettenger R, Rianthavorn P, Tsai E, Malekzadeh M. Preemptive plasmapheresis and recurrence of focal segmental glomerulosclerosis in pediatric renal transplantation. 
Pediatr Transplantation 2011: 15: 495–501.

Ultrasound and the diagnosis of renal and ureteral calculi

We retrospectively compared ultrasound examination with plain film radiography of the abdomen (KUB) in the diagnosis of renal and ureteral calculi in 13 patients. Overall, ultrasound was more sensitive than KUB (84% versus 54%) in detecting calculi. However, KUB was superior for the diagnosis of ureteral stones. No calculi were detected by intravenous urography that were not first seen on either ultrasound or KUB. Our experience suggests that the combination of ultrasound and KUB is less invasive and more sensitive than intravenous urography for the diagnosis of calculi in patients with symptoms and signs suggestive of stone disease or who are at high risk for stone formation.

Hypertension after renal transplantation in children

Hypertension persisted for longer than 6 mo or developed de novo after the first month following transplantation in seven of 77 pediatric recipients of renal allografts; concomitantly there were an elevation of PRA and renal angiographic abnormalities. In two of the four patients who developed RAS there was evidence of diminished allograft function. Successful correction of the stenotic lesion in these two recipients resulted in a return of the blood pressure, PRA, and biochemical function of the allograft to normal. Unsuccessful attempts at surgical repair led to loss of the allograft in the other two patients with RAS. Intrarenal vascular and/or parenchymal lesions were evident in the other three recipients with hypertension. Although an explanation was not apparent, subclinical rejection was hypothesized. Treatment effected reduction of the hypertension in these three patients and no deterioration of allograft function was observed for periods of 5, 34, and 38 mo, respectively. Renal angiographic studies and determinations of PRA are recommended in any pediatric recipient of an allograft who develops hypertension after the first month following transplantation or has hypertension which persists for longer than 6 mo after transplantation.

Renal artery stenosis in pediatric transplant recipients.

From 1967 through 1985, 400 cadaveric transplants were performed at Children Hospital of Los Angeles. Of these 400, 31 were later identified as having renal artery stenosis. No live related graft developed RAS. Of the 31 grafts, 11 were from donors less than 2 years of age. The major feature suggesting stenosis was hypertension: either persistent or a sudden exacerbation often associated with hypertensive encephalopathy. In individuals with hypertension without obvious cause, renal angiography should be promptly conducted under controlled conditions to avoid complications. The stenotic lesion involved 13 end-to-end and 19 end-to-side arterial anastomoses. Surgery for revascularization of RAS was performed in 21 of 31 with success or improvement in 14, no change in 2, and graft loss in 5. Percutaneous transluminal angioplasty was performed in 4. Two were unsuccessful, 1 was successful and 1 graft was lost. The 7 remaining patients were treated medically.

A novel treatment regimen for BK viremia.

Background BK viremia, a prerequisite for BK virus nephropathy (BKVN), affects 5% to 16% of pediatric renal transplant recipients (PRTR). We evaluated the safety and efficacy of a novel approach to treating BK viremia using fluoroquinolones and leflunomide in PRTR. Methods We studied 230 PRTR at Mattel Children’s Hospital, UCLA, who underwent renal transplantation between January 2003 and October 2010. Nineteen patients were found to have BK viremia. Ciprofloxacin was started when the BK viral load was greater than 625 copies/mL, and patients were switched to leflunomide if BK viral load did not decrease after 2 months of ciprofloxacin therapy. All patients underwent transplant kidney biopsy, and their estimated glomerular filtration rate (eGFR) and BK PCR was measured serially. The side effects of ciprofloxacin and leflunomide were recorded in each patient. Results There was a significant decrease in BK viral load in patients treated with ciprofloxacin and leflunomide (P<0.001) with only a small reduction in immunosuppression. BK viremia was associated with a significantly decreased eGFR (P<0.001), and treatment with ciprofloxacin and leflunomide was associated with improved eGFR (P<0.001). This approach resulted in a BKVN rate of only 1%. Conclusions This analysis demonstrates for the first time that, used in a stepwise fashion, ciprofloxacin and leflunomide are effective and safe treatments for BK viremia in PRTR.