Update on Pediatric Hemodialysis Adequacy.

The use of high reflux dialyzers to achieve a Kt/Vurea above 1.2 did not improve patient survival in most literature reports. After an electronic search in many sites, guidelines, systematic reviews, and review articles (cited references): We recommend (1) using the equilibrated double-pool, weekly rather than per session, Kt/Vurea, (2) Use of UF-dry weight to avoid V changes, (3) consider protein catabolic Rate (4) Use of double pool to avoid urea generation rebound effect. Beyond the urea model, other recommended parameters include the middle molecule clearance and patient clinical data as blood pressure control, normal ventricular morphology, and function, absence of anemia, bone mineral disease, vascular calcifications, good nutrition and growth, long-lasting vascular access, less intra-dialysis hypotension, fewer hospitalizations related to complications as infection, long-term patient survival with better life quality. All mentioned parameters are the good markers for adequate dialysis. Since (1) frequent short and (or) slow long dialysis sessions show better solute clearance and hemodynamic stability associated with better control of cardiovascular and bone disease, anemia, nutrition, and growth with better quality of life and survival. (2) The spare in the cost of the antihypertensive medications, erythroid-stimulating drugs, phosphate binders, and frequent hospitalization, compensates for the high dialysis cost. (3) The use of some advisable techniques can minimize access trauma; therefore, HD Model can be changeable according to each patient's clinical and biochemical follow-up dialysis adequacy progress pattern.

Management of recurrent focal segmental glomerulosclerosis (FSGS) post renal transplantation.

BACKGROUND: One of the common GN causing ESKD is focal segmental glomerulosclerosis (FSGS). Recurrence of FSGS post-transplantation can lead to graft loss. Data on management either prophylactically or once recurrence occurs are limited. This review article aims to assess the effective management of patients with FSGS recurrence post-transplantation, looking mainly at recurrence post prophylactic treatment and remission in case of treatment post recurrence. METHODS: Twenty-three studies were included using the search MeSH terms "FSGS" "recurrence" "adults" "transplantation" "treatment". Search engines used were Pubmed, clinical key, Scopus and Cochrane library. Inclusion criteria were articles covered adult patients with recurrent FSGS post renal transplantation, treatment with rituximab and plasmapheresis, and articles published from 2000 tt2021. Excluded articles were paediatric population, studies with no reported outcomes of the treatment of FSGS, and Patients who received stem cell transplantation or galactose therapy. RESULTS: Prophylactic PP did not show a reduction in recurrence of FSGS in 2/3 studies. Prophylactic rituximab was shown to reduce recurrence of FSGS in one-study and case reports. Treatment of recurrent FSGS with PP showed responses ranging from 41% to 100%. Only one study did not show improvement with PP use as treatment having a 27% remission. Treatment with rituximab showed variable results, with reports showing remission ranging from 57% to 100%. Whereas other reports showing no response at all. PP prescription reporting was variable. One study suggested intensified PP regimen while in most other studies PP was guided by the response reflected by the reduction of proteinuria. DISCUSSION: Reviewing the treatment of recurrent FSGS is crucial, as there no consensus on treating FSGS as the disease is not very common in the adult population. The evidence of different modalities is based on small cohort studies. This paper supports the use of PP and RTX as treatment of recurrent FSGS. CONCLUSIONS: In conclusion, PP and RTX are the main modalities to treat recurrent FSGS with varying response rates. Prophylactic PP does not play a role in preventing recurrent FSGS. Prophylactic rituximab might play a role in preventing FSGS post-transplantation. PP and RTX, when used as a treatment, show variable response rates. Larger RCTs are needed to have a strong level of evidence to base our clinical management on.

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.

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.

Rabbit anti-thymocyte globulin (rATG) versus IL-2 receptor antagonist induction therapies in tacrolimus-based immunosuppression era: a meta-analysis.

BACKGROUND: The aim of this meta-analysis is to explore the effect of IL-2RA vs rATG on the rate of acute rejection, post-transplant infections, and graft as well as patient's survival in standard- and high-risk renal transplant patients receiving tacrolimus-based maintenance immunotherapy. METHODS: Random effects model was the method used for identifying risk difference. Confidence interval including the value 1 was used as evidence for statistically significant risk difference. Heterogeneity was assessed using Der Simonian analysis. Heterogeneity was evident at the level of P value < 0.1 RESULTS: The random effects model showed no significant differences in both acute rejection rates between IL-2RA and rATG induction therapies with relative risk of 1.24 graft survival with relative risk 0.90. Patient survival also did not demonstrate any significant difference with a relative risk of 1.19. Random effects for CMV infection showed a lesser tendency for CMV infection in IL-2RA group compared to ATG group the with a relative risk of 0.73.In subgroup analysis, the random effects model for acute rejection rates in high-risk transplants showed a higher risk of acute rejection in the IL-2RA group compared to rATG (relative risk equals 1.55) In standard-risk transplants, there were no significant differences between both groups with relative risk equals 1.02 CONCLUSIONS: This meta-analysis revealed no significant difference in patient and graft survival when using IL-2RA vs rATG with the tacrolimus-based maintenance immunosuppression era. However, subgroup analysis showed less incidence of rejection in high-risk renal transplant recipient's population using rATG compared to IL-2RA.

Implication of interleukin-2 receptor antibody induction therapy in standard risk renal transplant in the tacrolimus era: a meta-analysis.

BACKGROUND: Interleukin-2 (IL-2) antagonist has been used as an induction therapy in many centres in calcineurin inhibitor-sparing regimens. Tacrolimus has overwhelmingly replaced cyclosporine in the maintenance immunosuppressive protocols in many transplant centres. The aim of our study and meta-analysis is to explore the effect of IL-2 induction therapy on the rate of rejection and patient and graft survival in standard-risk renal transplant patients with tacrolimus-based maintenance immunotherapy. Secondary aims included assessment of the effect of IL-2 induction therapy on creatinine change and the risk of cytomegalovirus (CMV) infection. METHODS: We conducted a systematic review in different databases to identify studies and research work that assessed the effect of IL-2 antibody induction therapy on renal transplant outcomes. Inclusion criteria for our meta-analysis were all studies that compared IL-2 induction therapy with placebo or no induction therapy in standard-risk renal transplant recipients on tacrolimus-based maintenance immunosuppressive therapy. Data collected were the name of the first author, journal title, year of publication, country where the study was conducted, number of patients in the IL-2 induction therapy arm and in the placebo arm, number of patients who had biopsy-proven rejection and graft survival in each arm. A random effects model was used for the meta-analysis. RESULTS: Of the 470 articles found in different databases, 7 were included in the meta-analysis. Forest plot analysis for rate of rejection during the follow-up period post-transplant showed no significant difference between the groups. There was no evidence of heterogenicity between included studies (I 2 = 21.8%, P = 0.27). The overall risk difference was -0.02 [95% confidence interval (CI) -0.05-0.01]. A random effects meta-analysis for patient and graft survival was performed using forest plot analysis and showed no significant effect of IL-2 receptor (IL-2R) antibody induction on patient or graft survival compared with placebo. The overall risk difference was -0.01 (95% CI -0.04-0.01) and 0.00 (95% CI -0.00-0.01), respectively. Three of the included studies showed no effect of basiliximab on creatinine change, two showed no effect on risk of CMV infection and two showed less risk of post-transplant diabetes in the basiliximab group. CONCLUSION: IL-2R antibody induction therapy has no significant effect on the rate of rejection or patient or graft survival in standard-risk renal transplant recipients on tacrolimus-based maintenance immunotherapy. More randomized controlled studies are needed.

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.

Validating the use of bioimpedance spectroscopy for assessment of fluid status in children.

BACKGROUND: Bioimpedance spectroscopy (BIS) with a whole-body model to distinguish excess fluid from major body tissue hydration can provide objective assessment of fluid status. BIS is integrated into the Body Composition Monitor (BCM) and is validated in adults, but not children. This study aimed to (1) assess agreement between BCM-measured total body water (TBW) and a gold standard technique in healthy children, (2) compare TBW_BCM with TBW from Urea Kinetic Modelling (UKM) in haemodialysis children and (3) investigate systematic deviation from zero in measured excess fluid in healthy children across paediatric age range. METHODS: TBW_BCM and excess fluid was determined from standard wrist-to-ankle BCM measurement. TBW_D2O was determined from deuterium concentration decline in serial urine samples over 5 days in healthy children. UKM was used to measure body water in children receiving haemodialysis. Agreement between methods was analysed using paired t test and Bland-Altman method comparison. RESULTS: In 61 healthy children (6-14 years, 32 male), mean TBW_BCM and TBW_D2O were 21.1 ± 5.6 and 20.5 ± 5.8 L respectively. There was good agreement between TBW_BCM and TBW_D2O (R2 = 0.97). In six haemodialysis children (4-13 years, 4 male), 45 concomitant measurements over 8 months showed good TBW_BCM and TBW_UKM agreement (mean difference - 0.4 L, 2SD = ± 3.0 L). In 634 healthy children (2-17 years, 300 male), BCM-measured overhydration was - 0.1 ± 0.7 L (10-90th percentile - 0.8 to + 0.6 L). There was no correlation between age and OH (p = 0.28). CONCLUSIONS: These results suggest BCM can be used in children as young as 2 years to measure normally hydrated weight and assess fluid status.

Tailgut cysts in children: a report of two cases and literature review.

Tailgut cysts are rare congenital lesions that typically manifest as a presacral, retrorectal, multicystic mass. Even though they are derived from remnants of the embryonic tailgut, they most often present in women. Differential diagnosis includes rectal duplication cyst, sacrococcygeal teratoma, and anterior meningocele. Treatment demands complete excision to prevent infection and malignant degeneration. Fewer than 20 pediatric cases have been reported. Two further affected children are described, one of whom presented uniquely with urinary tract obstruction and acute renal failure.

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.

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.