Search Results (65)

IgA nephropathy is the most common primary glomerulonephritis, with pathohistological changes described by the Oxford classification, while the Banff classification is used in transplant pathology. This study included 253 patients with IgA nephropathy in native kidneys, divided into the pediatric (n = 105) and adult (n = 148) groups. It aimed to examine clinical, and Oxford and Banff morphological parameters in relation to age, correlations of clinical data with pathohistological parameters, and predictors of the disease outcome. Pediatric patients more frequently presented with macroscopic hematuria, while adults showed higher urea and creatinine levels, and lower eGFR. Examining Oxford classification parameters, chronic glomerular and tubulointerstitial lesions were more common in adults. Banff parameters revealed more frequent chronically active glomerular, inflammatory, chronic tubulointerstitial, and vascular lesions in adults. All inflammatory, chronic tubulointerstitial, and vascular parameters correlated with serum urea levels, eGFR and CKD stage in adults, while less frequent in pediatric patients. Tubulointerstitial Oxford and Banff parameters were strong predictors of CKD and proteinuria progression in children, while such predictors were fewer in adults; segmental glomerulosclerosis predicted hematuria progression in adults. Banff parameters (cg, t, ti, i, i-IFTA, ptc, cv), not in Oxford classification, significantly predict outcomes and are recommended for incorporation into IgA nephropathy reports. Full article

Cystinosis is a rare systemic disease characterized by the accumulation of cystine in tissues, leading to multi-organ damage. Infantile nephropathic cystinosis is the dominant and severe form of cystinosis with critical renal manifestations that require kidney transplantation at an early age if left untreated. Cysteamine, the lifelong cystine-depleting therapy, is the mainstay treatment of nephropathic cystinosis. Cysteamine prevents cystine crystal formation and delays disease progression. While the initially introduced cysteamine consists of an immediate-release (IR) formulation, a delayed-release (DR) formulation has been developed with a simplified dosing regimen (Q12H instead of Q6H) and an improved quality of life while maintaining comparable efficacy. Due to the rare incidence of the disease and lack of international guidelines, diagnosis and treatment initiation are oftentimes delayed, leading to a poor prognosis. Pediatric and adult nephrologists from Kuwait, Saudi Arabia, the United Arab Emirates (UAE), and Qatar, in addition to one international expert from Amsterdam, convened to share their clinical experience, reflecting on the challenges encountered and therapeutic approaches followed in the management of nephropathic cystinosis in the Gulf Cooperation Council (GCC) region. Experts completed a multiple-choice questionnaire and engaged in structured discussions, where they shed light on gaps and limitations with regard to diagnostic tests and criteria to ensure early diagnosis and timely treatment initiation. Based on available literature, experts suggested an algorithm to help guide nephropathic cystinosis management in the GCC. It is highly recommended for patients who do not tolerate IR-cysteamine and do not adhere to IR-cysteamine treatment to switch to DR-cysteamine. Given the systemic nature of the disease, a multi-disciplinary approach is required for optimal disease management. Full article

Background: Kidney transplantation is the treatment of choice for pediatric patients with end-stage kidney disease. However, transplantation in children weighing < 15 kg remains challenging due to limited donor availability and higher surgical and medical risks. We report our 35-year single-center experience in this population, focusing on perioperative and long-term outcomes. Methods: We retrospectively analyzed kidney transplants performed from 1987 to 2023 in children weighing < 15 kg. Data on demographics, donor type, complications, immunosuppression, and outcomes at 2, 5, and 10 years (including survival, graft function, rejection, infections, and urological issues) were collected. Outcomes were compared between deceased and living donors and between recipients weighing < 10 kg and ≥10 kg. Results: Ninety-six transplants were included (mean age 3.3 years; mean weight 11.1 kg), 80 from deceased and 16 from living donors. Most patients (69.8%) had been treated with peritoneal dialysis. Median follow-up was 120 months. Patient survival was 95.8%; graft survival was 78.1%. Eight grafts (8.3%) were lost to renal vein thrombosis, all in deceased-donor recipients (p = 0.60). Preserved renal function (eGFR > 60 mL/min/1.73 m²) declined from 80.4% at 2 years to 66.0% at 5 years and 18.0% at 10 years. Graft survival at 10 years was significantly lower in children < 10 kg vs. ≥10 kg (49.6% vs. 80.3%, p = 0.003). CAKUT was associated with higher urological complication rates (p = 0.017). No significant differences emerged between living and deceased donor groups. Conclusions: Transplantation in children < 15 kg is feasible with good outcomes, but those <10 kg present lower graft survival at 10 years. Multidisciplinary assessment and center experience are key to optimizing results. Full article

While the pathogenic role of donor-specific anti-HLA antibodies (DSAs) in long-term immune-mediated injury after kidney transplantation is well established, the clinical relevance of non-donor-specific antibodies (nDSAs), also detected in transplant recipients, remains a subject of debate. This retrospective study evaluated the prognostic value of nDSAs in 92 pediatric kidney transplant recipients (89.1%, 9.8%, and 1.1% for first, second, and third transplants, respectively) at the University Hospital of Padua between January 2015 and December 2022, investigating the association between antibody development and clinical outcomes, including graft function, rejection episodes, and viral infections. Clinical, immunological, virological, and histopathological data were collected at 6, 12, and 24 months post-transplant. Antibody prevalence increased over time, with nDSAs being more frequent than DSAs at all timepoints. The combined presence of DSAs and nDSAs significantly increased the risk of ABMR (HR = 45.10; p < 0.001). Isolated nDSAs and DSAs were also associated with an increased risk of ABMR (HR = 6.43 and 12.10, respectively), suggesting a synergistic alloimmune effect. Viral infections also emerged as relevant cofactors in humoral alloimmunity. EBV viremia and intrarenal Parvovirus B19 (PVB19) infection were significantly associated with ABMR, with PVB19 also correlating with nDSA formation. In conclusion, integrated immunological and virological monitoring may support risk stratification and guide individualized post-transplant management. Larger multicenter studies are warranted to define the long-term impact of nDSAs in pediatric kidney transplantation. Full article

Cryptococcosis, an opportunistic fungal infection predominantly caused by Cryptococcus neoformans, is the third most common invasive fungal disease in solid organ transplant recipients. While well-characterized in adult kidney transplant (KT) patients, pediatric data remain sparse. This article compares clinical presentation, immune response, renal involvement, and management strategies of cryptococcosis between adult and pediatric KT recipients. In adults, the disease typically presents as cryptococcal meningitis or pulmonary infection, often complicated by delayed diagnosis and high mortality. In contrast, children frequently exhibit non-specific respiratory symptoms or disseminated disease, reflecting immune immaturity and increased susceptibility to hematogenous spread. Key immunopathological differences include impaired Th1 type responses, macrophage dysfunction, and variable complement activity across age groups. Management involves similar antifungal regimens such as liposomal amphotericin B, flucytosine, and fluconazole, but requires weight-based dosing and careful toxicity monitoring in pediatric patients. Early diagnosis through serum cryptococcal antigen screening, appropriate adjustment of immunosuppressive therapy, and coordinated multidisciplinary care are essential. The findings underscore the need for pediatric specific research and clinical vigilance, emphasizing tailored antifungal dosing and individualized immune management to improve outcomes in this vulnerable population. Full article

Genetic profiling and molecular biology methods have made it possible to study the etiology of the end-stage organ disease that led to transplantation, the genetic factors of compatibility and tolerance of the transplant, and the pharmacogenetics of immunosuppressive drugs and allowed for the development of monitoring methods for the early assessment of allograft rejection. This study aims to report the design and baseline characteristics of an integrated personalized genetic approach in solid organ transplantation, including whole-exome sequencing (WES) and the monitoring of dd-cfDNA by dPCR. Preliminary results reported female recipients with male donors undergoing two pediatric and five adult kidney and three heart transplantations. WES revealed a pathogenic mutation in RBM20 and VUS in TTN and PKP2 in heart recipients, while kidney donors presented mutations in UMOD and APOL1 associated with autosomal-dominant kidney diseases, highlighting the risks requiring the long-term monitoring of recipients, donors, and their family members. %dd-cfDNA levels were generally stable but elevated in cadaveric kidney recipient and one pediatric patient with infectious complications and genetic variants in the ABCB1 and ABCC2 genes. These findings highlight the potential of combining genetic and molecular biomarker-based approaches to improve donor–recipient matching, predict complications, and personalize post-transplant care, paving the way for precision medicine in transplantation. Full article

Background/Objectives: While there are several debates on en bloc renal transplants and pediatric donors regarding the efficacy and concern for renal mass, multiple studies have supported the notion that transplanting pediatric en bloc kidneys produces comparable results in contrast to single kidneys from living or deceased donors. Methods: This case series included a retrospective analysis of a university medical center, primarily focused on comparing the post-operative outcomes between recipients of pediatric and adult en bloc kidneys, which are horseshoe kidneys, from deceased donors and recipients of single adult kidneys from living or deceased donors. Results: This study demonstrated that the post-operative results in recipients of pediatric en bloc kidneys consisting of serum creatinine and estimated glomerular filtration rate (eGFR) values were lower and higher, respectively, and had a comparable improvement in kidney function at post-transplant, 1-week, 1-month, 3-months, and 1-year post-op marks. Conclusions: Our center data and outcomes indicate that en bloc kidney transplantation from pediatric donors yields comparable results to that of single kidney transplantations from living and deceased donors. Full article

Polyomavirus BK (BKPyV)-associated nephropathy (BKPyV-nephropathy) remains a significant cause of premature kidney allograft failure. In the absence of effective antiviral treatments, current therapeutic approaches rely on immunosuppression (IS) reduction, possibly at the risk of inducing alloimmunity. Therefore, we sought to explore the long-term effects of a tailored viro-immunologic surveillance and treatment program for BKPyV on the development of alloimmunity and kidney graft outcome. Forty-five pediatric kidney transplant recipients were longitudinally monitored for BKPyV replication, virus-specific immunity, and donor-specific HLA antibodies (DSAs). DNAemia developed in 15 patients who were treated with stepwise IS reduction. Among the other 30 patients, 17 developed DNAuria without DNAemia and 13 always resulted as BKPyV-negative. All patients with DNAemia cleared BKPyV after having mounted a virus-specific cellular immune response, and no biopsy-proven BKPyV-nephropathy was observed. The presence of cytotoxic populations directed to the BKPyV Large-T (LT) antigen early after transplantation protected kidney recipients from developing BKPyV replication, and the appearance of LT-specific T cells in viruric patients prevented the development of BKPyV-DNAemia. In our cohort, no significant correlation was observed between BKPyV-DNAemia and the development of DSA and antibody-mediated rejection. However, patients who experienced and cleared BKPyV-DNAemia had a worse allograft survival at a median follow-up of 18.9 years (p = 0.048). These data need to be confirmed in larger cohorts. Full article

Antibody-mediated rejection (AMR) is the leading cause of premature kidney transplant failure. The role of alloantibodies against Human Leukocyte Antigens (HLA) has been a primary focus in AMR. More recently autoantibodies and alloantibodies against the angiotensin II receptor type 1 (AT1R) and the endothelin A receptor (ETAR) have been linked to poor allograft outcomes in kidney transplantation. Nevertheless, evidence supporting routine testing remains insufficient. ELISA testing for anti-AT1R and anti-ETAR antibodies was performed in a pediatric renal transplant cohort. We selected 12 pediatric recipients who had undergone protocol biopsies and antibody measurements at 6 and 24 months post-transplant. Immunohistochemistry was performed on biopsies for AT1R and ETAR as well as the adhesion molecules ICAM-1 and VCAM-1. The analysis showed that ICAM-1 and VCAM-1 expression was significantly increased, along with the presence of circulating antibodies, in patients at 24 months post-transplant compared to patients without circulating antibodies. The presence of anti-AT1R and anti-ETAR antibodies does not seem to influence the expression of their receptors in the transplanted organ. Instead, the increase in adhesion molecules may precede the development of histological damage. Therefore, enlarging the cohort and extending long-term observation would help to understand the impact of anti-AT1R and anti-ETAR antibodies after transplantation. Full article

Background: Diarrhea frequently occurs after vascular organ transplantation, including kidney transplants. This may result from non-infectious factors, adverse effects of immunosuppressive medications, or infections caused by various pathogens, including viruses, bacteria, fungi, or parasites, for example, intestinal protozoan parasites such as Cryptosporidium spp., which are particularly dangerous for immunocompromised patients. Methods: This review is based on scientific articles sourced from validated databases such as PubMed, the National Center for Biotechnology Information (NCBI), ScienceDirect, and Google Scholar. The primary search was conducted on 12–13 July 2024, using the keywords ‘Cryptosporidium’ AND ‘cryptosporidiosis’ AND ‘kidney’ AND ‘transplant’ AND ‘adult’. Inclusion criteria encompassed human studies, case reports, peer-reviewed journal publications, review articles, and research articles in English. Exclusion criteria included studies not in English, gray literature (e.g., conference proceedings and abstracts), and data related to pediatric patients (under 18 years old) and HIV patients. Results: This systematic review and meta-analysis have highlighted an often-overlooked connection between Cryptosporidium spp. infections in adult kidney transplant recipients (KTR). Furthermore, it includes an analysis of the clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in these patients, based on available case reports. Our study demonstrates that adult kidney transplant patients are at a significantly higher risk of acquiring Cryptosporidium spp. compared to healthy participants. Conclusions: Cryptosporidium spp. infections can be asymptomatic, making it essential to screen both symptomatic and asymptomatic kidney transplant recipients. The clinical presentation of cryptosporidiosis typically involves digestive symptoms and can be complicated by biliary tract involvement. In KTR patients presenting with diarrhea, it is crucial to not only test for Cryptosporidium spp. but also to rule out bacterial and viral etiologies, including infections such as C. difficile, C. colitis, Clostridium spp., and rotavirus. The diagnosis of Cryptosporidium spp. infections primarily relies on microscopic methods, which are known for their low sensitivity. Therefore, diagnostic approaches should include both direct methods and, where possible, molecular techniques. Based on the analyzed cases, the most effective treatment results were achieved with reduction in immunosuppression if possible (strong, very low) and nitazoxanide at a dose of 500 mg twice daily for 14 days. Considering the public health implications of our findings, the current epidemiological data underscore the need for further research to develop effective prevention and intervention strategies against cryptosporidiosis. Preventive measures, regular screening programs, and the treatment of Cryptosporidium spp. infections should be integrated into the clinical care of transplant patients. It is also important that patients are informed about environmental risk factors. Full article

Background/Objectives: Kidney transplantation is the treatment of choice for children with end-stage renal disease (ESRD), but its outcome can be affected by urological complications, with incidence rates of 2.5–25%. The aim of this study was to evaluate the occurrence of urological complications and their management in a cohort of pediatric kidney transplant recipients. Materials and Methods: A retrospective analysis on 178 patients who received a renal transplant at our Pediatric Kidney Transplant Center between 2011 and 2023 was conducted. Demographic and clinical data were analyzed. Urological complications were categorized as early, intermediate, or late based on their onset time. Results: Out of 178 patients, 28 (15.7%) experienced urological complications. Most patients (61%) had a pre-existing uropathy. Early complications (7–30 days) were all obstructive, namely, ureterovesical junction obstruction and perirenal collections. Intermediate complications (1–3 months) comprised ureteral stenosis, symptomatic vesicoureteral reflux (VUR), and obstructive lymphocele. Late complications (>3 months) included symptomatic VUR and ureteral stenosis, with one case leading to ureteral rupture. Early complications were often detected due to acute graft dysfunction, while late ones were mainly identified during routine clinical, laboratory, or ultrasound follow-up. Urological complications requiring surgical or endoscopic therapy were 13.4%. Most ureteral stenoses were treated with initial endoscopic stents, followed by definitive surgery. VUR was treated with endoscopic correction with a high success rate (75%), while open surgery was reserved for cases where initial treatments failed or complications recurred. No clear correlations were found between patient characteristics and risk of urological complication. Urological complications required multiple diagnostic procedures and therapeutic interventions (+2.5 admissions in mean and approximately +EUR 24,000) compared to an uncomplicated post-transplant course. However, they did not significantly impact transplant outcomes, with a graft survival rate comparable to that of the control group. Conclusions: Regular post-transplant follow-up is crucial, especially for patients with known risk factors, to allow for timely detection and treatment of urological complications, avoiding detrimental effects on graft function and improving transplantation outcomes. Full article

Fluid overload significantly increases morbidity and mortality in critically ill children. Following hematopoietic cell transplant (HCT), children are at a high risk of fluid accumulation due to essential increased fluid intake for nutrition, blood products, and antimicrobials. In addition, many complications predispose these children to capillary leak and fluid overload (FO), such as sinusoidal obstruction syndrome, engraftment syndrome, sepsis, and acute kidney injury (AKI). FO > 10% occurs in nearly half of children following HCT and is associated with a lower PICU survival rate. In addition, in children with acute respiratory failure post HCT, each 1% increase in cumulative fluid balance on d 3 increases the odds of PICU mortality by 3%. Furthermore, FO worsens AKI. Tools such as the renal angina index and urinary biomarkers such as neutrophil gelatinase-associated lipocalin can help identify patients at risk of AKI and FO. Early detection, prevention, and intervention are crucial to improving outcomes in this population. Management strategies include fluid restriction, diuretics, and continuous kidney replacement therapy (CKRT) when FO exceeds 10% and other measures have failed. Full article

Safely expanding the use of extended-criteria organ donors is critical to increase access to kidney transplantation and reduce wait list mortality. We performed a retrospective analysis of 24 pediatric en-bloc (PEB) compared to 13 dual-kidney transplantations (DKT) and 39 living donor kidney transplants (LDKT) at the University of Virginia hospital, performed between 2011 and 2019. All living donor kidney transplants were performed in 2017. This year was chosen so that 5-year outcomes data would be available. Primary outcomes were glomerular filtration rate and serum creatinine at 12 and 24 months postoperatively. Secondary outcomes were patient and graft survival. The 1-year creatinine levels (mL/min/1.73 m²) were lower in the PEB group (median 0.9, IQR 0.8–1.4) when compared to the DKT (median 1.4, IQR 1.2–1.5) and LDKT (median 1.3, IQR 1.1–1.5) groups (p < 0.001). The 2-year creatinine levels (mL/min/1.73 m²) were also lower in the PEB group (median 0.8, IQR 0.7–1.08) compared to the DKT (median 1.3, IQR 1.1–1.5) and LDKT (median 1.3, IQR 1.0–1.5) groups (p < 0.001). The glomerular filtration rates demonstrated similar results. Graft survival at 1, 3, and 5 years was 100/100/90, 100/92/69, and 96/96/91 for LDKT, DKT, and PEB, respectively (p = 0.27). Patient survival at 1, 3, and 5 years was 100/100/90, 100/100/88 and 100/100/95 for LDKT, DKT, and PEB, respectively (p = 0.78). Dual KT and PEB transplantation are two alternative techniques to safely expand the donor pool. PEB kidney transplantation, though technically more demanding, provides the best long-term graft function. Full article

Pediatric solid organ transplant (SOT) recipients face a challenging balance between immunosuppression and graft rejection. While Epstein–Barr Virus (EBV) and cytomegalovirus (HCMV) are known contributors to post-transplant lymphoproliferative disease and graft rejection, respectively, the roles of herpesvirus 6 and 7 (HHV6 and HHV7) and the impact of these herpesviruses on cytokine levels remain unclear, leading to gaps in clinical practice. In this associative study, we measured 17 cytokines using a Bio-Plex assay in a meticulously curated plasma sample pool (N = 158) from pediatric kidney and liver transplant recipients over a one-year follow-up period. The samples included virus-negative and virus-positive cases, either individually or in combination, along with episodes of graft rejection. We observed that the elevation of IL-4, IL-8, and IL-10 correlated with graft rejection. These cytokines were elevated in samples where HCMV or HHV6 were detected alone or where EBV and HHV7 were co-detected. Interestingly, latent EBV, when detected independently, exhibited an immunomodulatory effect by downregulating cytokine levels. However, in co-detection scenarios with β-herpesviruses, EBV transitioned to a lytic state, also associating with heightened cytokinemia and graft rejection. These findings highlight the complex interactions between the immune response and herpesviruses in transplant recipients. The study advocates for enhanced monitoring of not only EBV and HCMV but also HHV6 and HHV7, providing valuable insights for improved risk assessment and targeted interventions in pediatric SOT recipients. Full article

Chronic kidney disease (CKD) is a significant challenge for pediatric endocrinologists, as children with CKD may present a variety of endocrine complications. Growth failure is common in CKD, and its severity is correlated with the degree of renal insufficiency. Management strategies include addressing reversible comorbidities, optimizing nutrition, and ensuring metabolic control. Kidney replacement therapy, including transplantation, determines a significant improvement in growth. According to a recent Consensus Statement, children with CKD stage 3—or on dialysis older >6 months—are eligible for treatment with recombinant growth hormone (rGH) in the case of persistent growth failure. Treatment with rGH may be considered for those with height between the 3rd and 10th percentile and persistent growth deceleration. In children who received kidney transplantation but continue to experience growth failure, initiation of GH therapy is recommended one year post-transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not an option. In children with CKD, due to nephropathic cystinosis and persistent growth failure, GH therapy should be considered at all stages of CKD. Potential adverse effects and benefits must be regularly assessed during therapy. Treatment with GH is safe in children with CKD. However, its general efficacy is still controversial. All possible problems with a negative impact on growth should be timely addressed and resolved, whenever possible with a personalized approach to the patient. GH therapy may be useful in promoting catch-up growth in children with residual growth potential. Future research should focus on refining effective therapeutic strategies and establishing consensus guidelines to optimize growth outcomes in this population. Full article