Diagnosis and Management of Atypical Hemolytic Uremic Syndrome In Children: Single Centre Experience

Atypical hemolytic uremic syndrome (aHUS) although rare is the commonest cause of acute renal failure (ARF) in children and has poor prognosis. We present single centre experience of aHUS. Thirty six children (29 males, 7 females) with mean age, 7.9 years presented with ARF, 2 children also had tonic–clonic type convulsions. Their hematology examination revealed hemolytic anemia with s. creatinine (SCr), 5.54 mg/dl. Acute HUS was observed in 75 %, acute on chronic HUS in 19.4 % and patchy cortical necrosis (PCN) in 5.6 % biopsies. Mean 5.4 plasma exchanges (PE) were carried out. Supportive management of anti-hypertensives and prednisone was also given. Recovery end points were establishment of urine output, improvement of SCr and hematological profile. Hematology and renal function profile improved variably in all children, 5.6 % died, relapse was observed in 80.5 % over mean 70 days; 13.9 % children are doing well over mean follow-up of 268.8 days. Thus poor prognosis was observed in 86.1 % children. Children with acute on chronic HUS and PCN did not recover. Six children who recovered had acute HUS. aHUS in Indian children occurs at an older age of around 8 years and chronic/irreversible changes on histopathology examination are harbingers of poor prognosis. PE is life-saving however further research for developing strategies to improve long-term survival is needed.     

Pre-transplant co-infusion of donor-adipose tissue derived mesenchymal stem cells and hematopoietic stem cells may help in achieving tolerance in living donor renal transplantation

Transplantation tolerance is still a Utopian dream for many transplanters. Mesenchymal stem cells (MSC) have shown immuno-modulatory and tolerogenic effects in experimental models. We present a 29-year-old male with end stage renal disease (ESRD) who was transplanted with HLA 4/6 matched kidney from 51-year-old father in June 2010 preceded by co-infusion of donor-adipose tissue derived mesenchymal stem cells (AD-MSC) and bone marrow derived hematopoietic stem cells (BM-HSC) under non-myeloablative conditioning for deleting rejecting T and B-cells. He has maintained fairly stable graft function with serum creatinine (SCr) between 1.5 and 1.8?mg/dL at 3 years post-transplant with absence of donor specific antibodies (DSA), normal protocol graft biopsy, and peripheral T-regulatory cell levels (pTregs) (CD127^low/?CD25^highCD4⁺) of 4.57% on zero immunosuppression since 6 months.     

Increasing access to renal transplantation in India through our single‐center kidney paired donation program: a model for the developing world to prevent commercial transplantation

Because access to transplantation with HLA‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end‐stage renal disease (ESRD) patient in India. We present a government and institutional ethical review board approved study of 56 ESRD patients [25 two‐way and 2 three‐way pairs] who consented to participate in KPD transplantation at our center in 2013, performed to avoid blood group incompatibility (n = 52) or positive cross‐match (n = 4). All patients had anatomic, functional, and immunologically comparable donors. The waiting time in KPD was short as compared to deceased donor transplantation. Laparoscopic donor nephrectomy was performed in 54 donors. Donor relationships were spousal (n = 40), parental (n = 13), others (n = 3), with median HLA match of 1. Graft survival was 97.5%. Three patients died with functioning graft. 16% had biopsy‐proven acute rejection. Mean serum creatinine was 1.2 mg/dl at 0.73 ± 0.32 months follow‐up. KPD is a viable, legal, and rapidly growing modality for facilitating LDRT for patients who are incompatible with their healthy, willing living donor. To our knowledge, this is the largest single‐center report from India.     

Effect of piriformis versus trochanteric starting point on fixation stability of short intramedullary reconstruction nails

Recently, a new, shorter IM nail using two 6 mm reconstruction screws for proximal fixation was introduced in two versions for femoral insertion: piriformis fossa (FAN) and greater trochanter (TAN). These nails were compared experimentally for their fixation stability, proximal load transmission, and failure strength in an unstable intertrochanteric fracture model in cadaveric femurs. Vertical and axial loads were first applied to the intact femurs. Fractures were created, subsequent fixation applied, and the femurs underwent a series of both vertical and axial loading tests. There was no significant difference in strain readings between the nails for either axial loading or cyclical loading. There was no statistically significant difference between the loads to failure for the trochanteric nails and the standard antegrade nails. The average ultimate loadfor the FAN and TAN nails were 3010 N and 2830 N respectively. These two nails performed very similarly throughout our testing.     

Allogenic hematopoietic stem cell transplantation in pemphigus vulgaris: a single-center experience

Background:

Pemphigus vulgaris (PV), an autoimmune disorder characterized by blistering skin/mucus membrane lesions, is mediated by desmoglein-3 autoantibodies. We carried out a prospective clinical trial of hematopoietic stem cell transplantation (HSCT) in thymus, bone marrow (BM) and periphery to reconstitute central and peripheral arms of self-tolerance.

Materials and Methods:

Eleven (M:F=5:6) patients with mean age 33.5 years and mean duration of disease 22.8 months, having painful pruritic blisters and ulcers resistant to corticosteroids, were treated with cytokine-stimulated allogeneic HSCT (mean dose: 21.8 × 10⁸ cells/kg BW) from blood group-matched related donors. BM with mean CD34+ count 1.1% was inoculated into thymus, marrow and periphery, followed by two peripheral blood stem cell (PBSC) infusions.

Results:

Recovery began within 24 hours of HSCT and new lesions stopped after 6 months. No graft versus host disease (GvHD)/adverse effect was observed in any patient/donor. Over a mean follow-up of 8.02 years, all patients were well without recurrence/new lesions.

Conclusion:

Drug-resistant PV can be successfully and safely treated by allogeneic HSCT.     

Successful treatment of Bronchiolitis obliterans with organizing pneumonia in dialysis patient

A 42-year-old end stage renal disease (ESRD) patient was admitted with fever, anorexia, malaise, non-productive cough, and dyspnea, of one-week duration. Multiple cultures of the blood, sputum, and urine were negative for microorganisms. The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when patient with pulmonary infiltrate did not respond to conventional antibiotic therapy and frequent hemodyalisis. High-resolution computed tomography of the chest revealed patchy air-space consolidation, ground-glass opacities, and small nodular opacities, predominantly located at the peripheral part of the lungs. Cultures and stains of bronchoalveolar lavage (BAL) specimen and bronchoscopic biopsy of lung tissue were negative for organisms [bacteria, mycobacterium tuberculosis, PCP, fungus, and atypical organism] and showed evidence of BOOP. Patient recovered completely with early diagnosis and treatment with steroids and underwent successful renal transplantation with wife as donor without postoperative complication and relapse.     

Outcome of renal transplantation in patients with diabetic nephropathy—a single-center experience

Background  

Type 2 diabetes mellitus (DM) is the commonest cause of end-stage renal disease (ESRD) worldwide. Data scarcity on renal transplantation (RTx) outcome in diabetic nephropathy (DN) prompted us to review our experience. This retrospective single-center, 5-year study was undertaken to evaluate patient and graft survival and function, evaluated by serum creatinine (SCr), rejection episodes, and mortality in patients.     

Deceased donor kidney transplantation in autosomal dominant polycystic kidney disease: a single-center experience

Renal transplantation (RTx) has become the treatment of choice for end-stage renal disease (ESRD) in autosomal dominant polycystic kidney disease (ADPKD), the most common genetic kidney disease. Because of the inheritable nature of this disease, live related donors might be avoided due to the fear of future appearance of polycystic disease. This retrospective singlecenter study was undertaken to evaluate patient/graft survival function vis-a-vis serum creatinine (SCr), rejection episodes and mortality in ADPKD vs matched control patients. Between 2000 and 2009, 18 (7.4%) deceased donor renal transplant (DDRTx) were performed for ESRD due to ADPKD. Diagnosis of ADPKD was established by family history and ultrasound. An individualized approach was applied for the need of pre-transplant nephrectomy. All recipients received rabbit-anti-thymocyte globulin induction and maintenance triple immunosuppression. Delayed graft function was observed in 33% patients, and 16% had biopsy-proven acute rejection. Over mean follow-up of 4.67 ± 2.2 years, patient and graft survival rates were 72.22% and 83.33%, with mean SCr (mg/dL) of 1.44 ± 0.54, 1.78 ± 0.42 and 2.2 ± 0.6 at 1, 5 and 10 years. Overall, 44.4% (n-8) underwent pre-transplant nephrectomy. Infection and cardio/cerebrovascular events were the main causes of death. Patient, graft survival and acute rejection were similar between ADPKD and control group. DDRTx in ADPKD has acceptable patient and graft survival. Because of the inheritable nature of the disease, and unavailability of genetic linkage analysis as a routine, DDRTx is a viable option to avoid using unrelated donors.     

Increasing access to kidney transplantation for sensitized recipient through three-way kidney paired donation with desensitization: The first Indian report

The combination of kidney paired donation (KPD) with desensitization represents a promising method of increasing the rate of living donor kidney transplantation (LDKT) in immunologically challenging patients. Patients who are difficult to match and desensitize due to strong donor specific antibody are may be transplanted by a combination of desensitization and KPD protocol with more immunologically favorable donor. We present our experience of combination of desensitization protocol with three-way KPD which contributed to successful LDKT in highly sensitized end stage renal disease patient. All recipients were discharged with normal and stable allograft function at 24 mo follow up. We believe that this is first report from India where three-way KPD exchange was performed with the combination of KPD and desensitization. The combination of desensitization protocol with KPD improves access and outcomes of LDKT.