Journey of a patient with scleroderma from renal failure up to kidney transplantation.

The increased awareness of systemic sclerosis (SS) and its pathogenetic background made the management of this disease more amenable than previously thought. However, scleroderma renal crisis (SRC) is a rarely seen as an associated disorder that may involve 2%-15% of SS patients. Patients presented with earlier, rapidly progressing, diffuse cutaneous SS disease, mostly in the first 3-5 years after non-Raynaud clinical manifestations, are more vulnerable to develop SRC. SRC comprises a collection of acute, mostly symptomatic rise in blood pressure, elevation in serum creatinine concentrations, oliguria and thrombotic microangiopathy in almost 50% of cases. The advent of the antihypertensive angiotensin converting enzyme inhibitors in 1980 was associated with significant improvement in SRC prognosis. In a scleroderma patient maintained on regular dialysis; every effort should be exerted to declare any possible evidence of renal recovery. A given period of almost two years has been suggested prior to proceeding in a kidney transplant (KTx). Of note, SS patients on dialysis have the highest opportunity of renal recovery and withdrawal from dialysis as compared to other causes of end-stage renal disease (ESRD). KTx that is the best well-known therapeutic option for ESRD patients can also be offered to SS patients. Compared to other primary renal diseases, SS-related ESRD was considered for a long period of poor patient and allograft survivals. Pulmonary involvement in an SS patient is considered a strong post-transplant independent risk factor of death. Recurrence of SRC after transplantation has been observed in some patients. However, an excellent post-transplant patient and graft outcome have been recently reported. Consequently, the absence of extrarenal manifestations in an SS-induced ESRD patient can be accepted as a robust indicator for a successful KTx.

Drug-Induced Myelosuppression in Kidney Transplant Patients.

Renal transplant is considered the best therapeutic option for suitable patients with end-stage kidney failure. Hematological complications that occur after kidney transplant include posttransplant anemia, leukopenia, neutropenia, and thrombocytopenia. Severely persistent leukopenia and neutropenia events predispose patients to infection, including opportunistic infections. The mainstay tactic for such complications is to reduce the burden of the immunosuppression by the offending agent, but this tactic is associated with increased risk of acute rejection. Given the absence of laboratory investigations to specifically identify the culprit, a complete withdrawal of these agents may be the ultimate diagnostic option. Future therapeutic strategies, however, should focus on reducing the immunosuppressive burden, the introduction of less myelotoxic agents, early recognition, and prompt treatment of infectious episodes. This will help in the optimization of the myelopoietic function and normalization of the hematological profile, resulting in better allograft and patient survival.

Bilateral progressive cystic nephroma in a 9-month-old male infant requiring renal replacement therapy.

We report the case of a 3-year-old boy who presented at 9 months of age with abdominal distension and was found to have a triad of bilateral cystic nephroma, pleuropulmonary blastoma (PPB) and juvenile intestinal polyps. There have been three previous reported cases of patients with the same associated diagnoses. Our patient is the first reported patient with PPB who received renal replacement therapy and progressed to successful renal transplantation. The potential increased risk of progression of malignancy of PPB (type 1) with immunosuppression following transplantation remains unknown.

Post-transplantation lymphoproliferative disorders: Current concepts and future therapeutic approaches.

Transplant recipients are vulnerable to a higher risk of malignancy after solid organ transplantation and allogeneic hematopoietic stem-cell transplant. Post-transplant lymphoproliferative disorders (PTLD) include a wide spectrum of diseases ranging from benign proliferation of lymphoid tissues to frank malignancy with aggressive behavior. Two main risk factors of PTLD are: Firstly, the cumulative immunosuppressive burden, and secondly, the oncogenic impact of the Epstein-Barr virus. The latter is a key pathognomonic driver of PTLD evolution. Over the last two decades, a considerable progress has been made in diagnosis and therapy of PTLD. The treatment of PTLD includes reduction of immunosuppression, rituximab therapy, either isolated or in combination with other chemotherapeutic agents, adoptive therapy, surgical intervention, antiviral therapy and radiotherapy. In this review we shall discuss the prevalence, clinical clues, prophylactic measures as well as the current and future therapeutic strategies of this devastating disorder.

Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options in de novo and recurrent diseases.

For decades, kidney diseases related to inappropriate complement activity, such as atypical hemolytic uremic syndrome and C3 glomerulopathy (a subtype of membranoproliferative glomerulonephritis), have mostly been complicated by worsened prognoses and rapid progression to end-stage renal failure. Alternative complement pathway dysregulation, whether congenital or acquired, is well-recognized as the main driver of the disease process in these patients. The list of triggers include: surgery, infection, immunologic factors, pregnancy and medications. The advent of complement activation blockade, however, revolutionized the clinical course and outcome of these diseases, rendering transplantation a viable option for patients who were previously considered as non-transplantable cases. Several less-costly therapeutic lines and likely better efficacy and safety profiles are currently underway. In view of the challenging nature of diagnosing these diseases and the long-term cost implications, a multidisciplinary approach including the nephrologist, renal pathologist and the genetic laboratory is required to help improve overall care of these patients and draw the optimum therapeutic plan.

Continuous venovenous hemofiltration with or without extracorporeal membrane oxygenation in children.

OBJECTIVES: We report the frequency of usage, patient demographics, and outcomes in children treated with continuous venovenous hemofiltration (CVVH) in three pediatric intensive care units (PICUs), with one unit providing combined extracorporeal membrane oxygenation (ECMO) and CVVH. DESIGN: Prospective database analysis. SETTING: Three regional PICUs in the Trent Haemofiltration Network with two general PICUs admitting 450-500 patients annually and the other providing regional cardiac support and a supraregional service for ECMO (600-650 admissions annually with 50 ECMO patients). PATIENTS: Children who underwent CVVH alone or in combination with ECMO or other therapies between January 2000 and December 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 115 children (58 male) treated, with a median age of 18 months (range 1 day to 17 yrs) and median weight of 12 kg (range 1.8-119 kg). In the two PICUs without ECMO, CVVH was undertaken in 2.5% of admissions annually compared with 3% of annual admissions to the PICU with an ECMO service. Fifty-five patients received CVVH alone (group 1), while 53 patients underwent CVVH in conjunction with ECMO (group 2). In addition, five patients received plasmafiltration followed by CVVH, and two patients were treated with combined CVVH and molecular adsorbents recirculating system. Mean duration of therapy in group 1 was 142 hrs (1-840 hrs) and in group 2,231 hrs (3-1104 hrs). Overall patient survival was 43% with 29 of 55 (53%) CVVH patients surviving and 18 of 53 (34%) of those treated with ECMO plus CVVH. CONCLUSIONS: Performing CVVH in a heterogeneous population with large age and weight ranges poses significant clinical and technical challenges. The low frequency of CVVH use, as well as the use of other extracorporeal therapies, also raises problems with maintaining nursing skills. Objective clinical and biochemical markers for commencing CVVH alone or in combination with ECMO remain to be defined.

Acute renal failure in children: etiology, treatment and outcome.

Children with acute renal failure (ARF) may be treated in pediatric renal or intensive care (PICU) units where there is an increasing use of continuous renal replacement therapies such as hemofiltration (HF). Over three years, we prospectively recorded details of all patients with ARF treated both within our regional pediatric renal unit, in two local neonatal intensive care units (NICUs), and one PICU, which are all supported by our institution. Our study included eighty-three ARF patients (43% male) with a median age of 5.7 years (range 1 day - 19.8 years); 41% of patients were < 2 years, 20% 2-5 years, 13% 5-10 years and 26% > 10 years of age. A total of 37 patients (45%) were treated in the renal unit versus 46 (55%) patients in NICU/PICU. The initial treatment modality was conservative in 33%, peritoneal dialysis (PD) in 23%, hemodialysis (HD) in 15%, HF in 28%, and isolated plasmafiltration in one percent of the patients. About 16% of the patients required more than one treatment modality. Outcome data at three months showed normal renal function in 49%, deaths in 20%, dialysis dependent disease in 14%, chronic renal failure (GFR < 60ml/min/1.73m2) in eight percent, and proteinuria and/or hypertension in seven percent of the patients. Only one (3%) death occurred in 37 patients treated in the renal unit compared to 16 deaths in 46 patients (35%) treated in the NICU/PICU. Our findings further confirm the low mortality rate with isolated renal failure and the substantial mortality and renal workload in intensive care areas where renal failure is often part of multi-organ failure. Further prospective studies will be required to analyze the impact of early hemofiltration in such patients.

Multicystic dysplastic kidney and pelviureteric junction obstruction.

Two infants with nonfunctioning antenatally detected multicystic dysplastic kidneys developed acute renal failure in conjunction with pelviureteric obstruction of the contralateral kidney at 9 and 14 months of age, respectively. The initial postnatal ultrasounds had shown mild pelvic dilatation in both cases. Clinicians need to be aware of the possibility of late obstruction. We suggest that it is good practice to review patients with antenatally detected urinary tract abnormalities and equivocal investigations at joint nephrouroradiology meetings.