Immune-mediated nephropathies in kidney transplants: recurrent or de novo diseases.

IMN contribute to ESRD in 13% children with renal transplant (txp). Recurrent or de novo IMN can cause graft dysfunction and/or failure, but the details regarding incidence, therapy, and outcome remain poorly understood. Retrospective single-center study of all pediatric kidney txp was carried out since 1998. Clinical presentation, pathology, therapy, and graft outcomes of children with recurrent or de novo IMN were reviewed. IMN was the primary etiology of ESRD in 28 of the 149 txp recipients. Eleven children had biopsy-proven post-txp IMN-six were recurrent and five had de novo. Presentation varied with changes in SCr and/or proteinuria. Initial therapy included higher doses of steroids, MMF, and tacrolimus. Outcome was excellent with only one late graft loss. Full remission was achieved in all other patients, but some had re-recurrence of the IMN. Median follow-up time was 11.8 years. IMN (recurrent or de novo) occurred in 7.4% (11 of 149) of all kidney txp performed at our center. IMN post-txp was often seen late post-txp, usually asymptomatic and noted to have relapsing pattern. Early diagnosis and prompt therapy resulted in excellent long-term outcome in children diagnosed with post-txp IMN.

Anuria since birth: does it impact outcome of kidney transplant in infants?

Kidney transplantation (txp) in infants has recently made much progress but provides a unique challenge in infants anuric since birth. Little data exists on outcome of renal txp recipients with anuria since birth. Retrospective chart review was done for outcome of 27 children with wt ≤15 kg and they were divided into two groups: Group A (N=21) with urine output and Group B (N=6) anuric since birth had their urological complications and long-term outcome compared. Median age at the time of txp 18 vs 23 months, mean wt 10.8 vs 11.8 kg, and mean ht 77 cm in both, mean follow-up post-txp: 9.4 vs 5.6 years, and neurological problems were noted in 48% and 33% in Group A and Group B. There was no graft thrombosis or post-transplant lymphoproliferative disease and only two rejections. Anuric Group B were older, had more post-txp urological surgeries (66% vs 19%) and UTIs (66% vs 38%) compared to Group A. The overall graft survival at 1, 5, and 10 years was 96%, 86%, and 70%; patient survival at 1, 5, and 10 years was 96%, 85%, and 85%. Long-term graft outcomes in small children, anuric prior to txp, were excellent despite higher rates for UTIs and urological complications.

Autoimmune polyglandular syndrome type I can have significant kidney disease in children including recurrence in renal allograft - a report of two cases.

BACKGROUND: Autoimmune polyglandular syndrome type 1 (APS 1) is an autosomal recessive disorder characterized by immune injury of multiple organ systems (primarily endocrine) secondary to a mutation in the autoimmune regulator (AIRE) gene. In some cases, patients develop tubulointerstitial nephritis (TIN) and progress to end-stage renal failure (ESRD). CASE DIAGNOSIS/TREATMENT: We describe two patients with APS 1 and TIN. In both cases, TIN was clinically silent and the diagnosis was confirmed by renal biopsy. In one patient, renal function remained stable with immunosuppressive therapy. A second patient progressed to ESRD despite treatment, and received a deceased donor allograft. TIN recurred in the transplanted kidney and was reversed successfully with rituximab. Severe, recurrent esophageal candidiasis also resolved. CONCLUSION: TIN is an important complication of APS 1 that may result in ESRD, and may recur in the transplanted kidney. TIN may be under-recognized, as the presentation is unapparent clinically and urinalysis remains normal. Immunosuppressive therapy may be effective and, therefore, routine monitoring of renal function is warranted in asymptomatic individuals.

Successful treatment of severe acute antibody-mediated rejection of renal allografts with bortezomib--a report of two pediatric cases.

aAMR in renal allografts is uncommon and remains a challenge as it is often refractory to treatment modalities. Aggressive therapy is essential to reverse the rejection as it results in renal allograft loss in approximately 27-40% of cases. There are anecdotal case reports of use of bortezomib, a proteasome inhibitor in the treatment of resistant AMR cases in solid organ transplant recipients; however, the experience is limited. We herein report successful reversal of resistant aAMR in two pediatric patients with bortezomib. Patients were initially treated with IV methylprednisolone pulse therapy with IVIG and PP three times weekly for a total of 10 treatments. After the standard therapy used at our institution persistence of DSA associated with graft dysfunction prompted the use of bortezomib to further treat the rejection. We did not have any neurologic side effects, but one patient did experience significant infections after bortezomib infusions requiring prolonged antimicrobial therapy. The long-term outcome of both children was excellent with preservation of normal renal function and persistent reduction in DSA titers.

Successful rescue of refractory acute antibody-mediated renal allograft rejection with splenectomy--a case report.

Highly sensitized patients receive fewer kidney transplants and have a high risk for severe rejection with increased rates of graft loss. We present a highly sensitized child who after desensitization protocol received a kidney transplant and developed refractory acute antibody-mediated rejection. He failed to respond to standard therapy and needed an urgent splenectomy as rescue therapy. Our patient, an 18-yr-old AA male with ESRD due to obstructive uropathy received a second DD transplant. The allograft functioned immediately with SCr 1.4 mg/dL on day #5. On day #8, he was re-admitted with fever, oligoanuria, and renal failure. He was started on methylprednisolone pulse, thymoglobulin, intravenous immunoglobulin, and PP. The transplant kidney biopsy revealed features suggestive of acute AMR. On day #14, the patient remained dialysis dependent with no response to therapy. He underwent an urgent splenectomy and a slow increase in urine output and GFR was noted. The SCr one month post-splenectomy was 1.1 mg/dL. At one yr post-txp, his GFR remained stable with SCr 0.9 mg/dL on tacrolimus, mycophenolate mofetil, and prednisone. Urgent splenectomy successfully reversed refractory acute AMR, in our highly sensitized patient with second renal transplant.

Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus.

We report the outcome of our single-center, long-term follow-up study of tacrolimus therapy in children with steroid-resistant nephrotic syndrome (SRNS). All cases of nephrotic syndrome (NS) with kidney biopsies treated at our center between January 2000 and July 2008 were reviewed. Children with systemic lupus erythematosus and steroid-dependent NS were excluded. Nineteen children with SRNS received tacrolimus. Histopathological analysis of the biopsy revealed the underlying conditions of these 19 patients to be focal segmental glomerulosclerosis (ten patients), C1q nephropathy (four), membranous nephropathy (two), minimal change disease (one), membranoproliferative glomerulonephritis (one), and immunoglobulin A nephropathy (one). The mean follow-up was 55 months, and the median age of the patient cohort was 10 years. We observed complete remission in 11 (58%) patients, partial remission in six (32%), and failure to respond in two (9%). The median time to response was 8 weeks. Side effects were mild and transient (one case of acute kidney injury and three cases of hyperglycemia). The initial rate for combined partial and complete remission of the NS in children with SRNS was 81%, which was sustained in 58% of the patients on follow-up. Among children with FSGS, the sustained remission rate was 50%, while 40% progressed to end-stage renal disease (ESRD) (mean time 52 months). Based on the results of this study, we conclude that tacrolimus is an effective and well-tolerated therapeutic option for the treatment of SRNS in children. However, the occurrence of relapses of the NS with progression to ESRD during the long-term follow-up indicates the need for careful monitoring of such patients.

A single-center study of C1q nephropathy in children.

C1q nephropathy (C1qN) is a rare idiopathic glomerulopathy typically seen in adolescents and young adults. All kidney biopsies done from 2002 to 2007 were analyzed (264). Thirteen cases of C1qN from 212 (6.6%) native biopsies and one case out of 52 (1.9%) transplant biopsies were reviewed regarding demographic features, clinical presentation, histopathology, treatment, and outcome. Age varied from 1 to 18 years; half were boys. Ten children (71.4%) presented with nephrotic syndrome (NS). The most common histopathology found was diffuse mesangial proliferative glomerulonephritis (DMP) by light microscopy (LM), with diffuse granular staining for C1q predominantly in the mesangium. Children with either NS or persistent gross hematuria received prednisone and angiotensin-converting enzyme inhibitors (ACEi) (11). Median follow-up was 36 months. Steroid response was complete in 6 patients (54.5%). Those with steroid resistance (5) or steroid dependence (2) received further immunosuppression with mycophenolate mofetil (MMF) or tacrolimus (Tac). Three children achieved complete remission and four partial remission. Frequent relapses were seen in 4/14 patients. Renal survival was 100%. Our report reveals a high incidence of C1qN in pediatric patients, with variable clinical presentation. Despite a high incidence of steroid resistance among those with NS, an excellent response was observed with the addition of further immunosuppression.

Donor-specific antibodies by flow single antigen beads in pediatric living donor kidney transplants: single center experience.

Flow PRA and SAB are now routinely performed to identify HLA antibodies in the recipient sera. The presence of DSA is considered a risk factor for graft failure. However, this risk is not clearly defined. We reviewed all the pediatric recipients of living donor kidney transplants since Flow PRA and Flow SAB became routinely done at our institution. All children had negative CDC and Flow XMs. Comparison of clinical outcome was done between those with and without pretransplant DSA. Six children had positive DSA by Flow SAB. They received thymoglobulin, steroids, tacrolimus, and MMF. Five had anti-HLA class I antibodies and one anti-HLA class II. Only one child had an AR. Graft survival: 100% at last visit with GFR >70 mL/min/1.73 m(2). A control group without DSA was used for comparison (n = 44). They received our standard protocol: basiliximab, tacrolimus, MMF, and steroids. AR rate was 9%. Both groups had similar follow-up time, and patient and graft survival rates. In our small series, we saw excellent outcome despite the presence of DSA pretransplant. No unequivocal ideal to establish the ideal immunosuppressive regimen for this cohort of patients has been established and the long-term outcome of these recipients has not been delineated.

Impact of laparoscopic donor nephrectomy on allograft function in pediatric renal transplant recipients: a single-center report.

Laparoscopic donor nephrectomy (LDN) is rapidly becoming the preferred technique for the procurement of living donor kidneys. An association of this technique with delayed graft function and higher risk for rejection has been reported in pediatric recipients. We reviewed our experience of 17 pediatric patients who received a living donor kidney, from 2002 to 2004, procured by LDN, and compared it with a matched group that received living donor kidneys harvested by the open technique. Patient demographics, etiology of renal failure, intra-operative events, length of stay, serum creatinine decline, and graft function were reviewed. Our experience confirmed the findings of earlier reports specifically in small pediatric recipients. The LDN group showed a significantly slower decline in creatinine in the immediate post-operative period and longer intra-operative time. However, there was no difference between the two groups in the length of hospital stay, and creatinine clearances at discharge, six, 12 and 24 months post-operatively. The incidence of acute rejection was similar in both groups. LDN is a safe procurement modality for pediatric patients. The risk for prolonged OR time and delay graft function has to be considered during the evaluation process.

C1q nephropathy in a child with a chromosome 13 deletion.

C1q nephropathy (C1qNP) is a rare cause of childhood nephrotic syndrome (NS). We describe a child with retinoblastoma, lipomyelomeningocele and a chromosome 13 deletion who presented with massive proteinuria due to C1qNP. Despite steroid resistance, successful treatment of the NS was achieved with mycophenolate mofetil.