Pediatric kidney transplants with multiple renal arteries show no increased risk of complications compared to single renal artery grafts

BackgroundKidney allografts with multiple renal arteries (MRA) are not infrequent and have been historically associated with a higher risk of developing vascular and urologic complications. Reports of kidney transplantation using MRA allografts in the pediatric population remain scarce. The aim of this study was to evaluate if transplantation of allografts with MRA with a surgical intent of creating a single arterial inflow using vascular reconstruction techniques when required, and without the routine use of surgical drains or ureteral stents, is associated with an increased risk of complications when compared to single renal artery (SRA) grafts.MethodsWe retrospectively analyzed all pediatric renal transplant recipients performed by a single surgeon at our center between January 2015 and June 2022. Donor and recipient demographics, intraoperative data, and recipient outcomes were included. Recipients were divided into two groups based on SRA vs. MRA. Baseline variables were described using frequency distributions for categorical variables and means and standard errors for continuous variables. Comparisons of those distributions between the two groups were performed using standard chi-squared and t-tests. Time-to-event distributions were compared using the log-rank test.ResultsForty-nine pediatric transplant recipients were analyzed. Of these, 9 had donors with MRA (Group 1) and 40 had donors with SRA (Group 2). Native kidney and liver mobilization was performed in 44.4% (4/9) of Group 1 vs. 60.0% (24/40) of Group 2 cases (p = 0.39). There were no cases of delayed graft function or graft primary nonfunction. No surgical drainage or ureteral stents were used in any of the cases. One patient in Group 2 developed a distal ureter stricture. The geometric mean serum creatinine at 6- and 12-months posttransplant was 0.7 */ 1.2 and 0.9 */ 1.2 mg/dl in Group 1 and 0.7 */ 1.1 and 0.7 */ 1.1 mg/dl in Group 2. Two death-censored graft failures were observed in Group 2, with no significant difference observed between the two groups (p = 0.48).ConclusionsOur study demonstrates that pediatric renal transplantation with MRA grafts, using a surgical approach to achieve a single renal artery ostium, can be safely performed while achieving similar outcomes as SRA grafts and with a low complication rate

Risk Assessment of Severe Congenital Anomalies of the Kidney and Urinary Tract (CAKUT): A Birth Cohort

Recent advances in the early diagnosis of fetal CAKUT with an increase in fetal surgical interventions have led to a growing number of neonatal survivors born with severe renal dysfunction. This, in turn, has required the development of multi-disciplinary treatment paradigms in the individualized management of these infants with advanced stage kidney disease from birth. Early multi-modal management includes neonatal surgical interventions directed toward establishing adequate urine flow, respiratory support with the assessment of pulmonary hypoplasia, and establishing metabolic control to avoid the need for dialysis intervention. The development of specialized imaging to assess for residual renal mass with non-invasive 3-dimensional techniques are rapidly evolving. The use of non-radioactive imaging offers improved safety and allows for early prognostic-based planning including anticipatory guidance for progression to end stage renal disease (ESRD). The trajectory of kidney function during the neonatal period as determined by peak and nadir serum creatinine (SCr) and cystatin C (CysC) during the first months of life provides a guide toward individualized prospective management. This is a single center experience based on a birth cohort of 42 subjects followed prospectively from birth for an average of 6.1 ± 2.8 years at the University of Miami/Holtz Children's Hospital during the past decade. There was an 8:1 male: female ratio. The birth cohort was divided into 3 subgroups according to CKD Stages at the current age: CKD 1–2 (Group 1) (eGFR ≥ 60 ml/min/1.73 m2) (N = 15), CKD stage 3–5 (Group 2) (eGFR ≤ 59 ml/min/1.73 m2) (N = 12), and ESRD—Dialysis and/or Transplantation (Group 3) (N = 15). A neonatal CysC >3.0 mg/L predicted progression to ESRD while a nadir SCr >0.6 mg/dL predicted progression to CKD 3–5 with the highest specificity and sensitivity by ROC-AUC analysis (P < 0.0001). Medical management was directed toward nutritional support with novel formula designs, early introduction of growth hormone and strict control of mineral bone disorder. One of the central aspects of the management was to avoid dialysis for as long as feasible with a primary goal toward pre-emptive transplantation

Case report: Bordetella holmesii: A rare pathogen causing infective endocarditis associated glomerulonephritis

Infective endocarditis (IE) can cause multiorgan dysfunction and chronic kidney disease, in addition to cardiac sequelae. The presentation may be vague and can manifest as acute glomerulonephritis. While the most common pathogens of infective endocarditis are Staphylococcus and Streptococcus species, we report a rare pathogen Bordetella holmesii causing infective endocarditis associated glomerulonephritis. A 20-year-old male patient with tetralogy of Fallot with pulmonary atresia and aortopulmonary collaterals underwent several cardiac surgeries including prosthetic pulmonary valve replacement in the past. He was admitted for 3 days at an outside hospital for fever, cough, and hemoptysis, and diagnosed with streptococcal pharyngitis, for which he received antibiotics. Five weeks later, he presented to our institution with lower extremity edema and gross hematuria. On examination, he was afebrile, normotensive, had a 7-kg weight gain with anasarca, and a systolic murmur, without rash. Investigations revealed elevated serum creatinine, nephrotic range proteinuria, hematuria, and hypocomplementemia, consistent with acute glomerulonephritis. Given his cardiac history, blood cultures were collected from three sites. Broad-spectrum antibiotics were initiated when he subsequently developed fever. Renal pathology on biopsy showed diffuse proliferative immune complex-mediated glomerulonephritis. Transesophageal echocardiogram visualized a vegetation on the pulmonary valve. Bordetella holmesii was ultimately cultured from the prior and current hospitalization. A serum sample detecting microbial cell-free DNA sequencing confirmed Bordetella holmesii at very high levels. After completing 6 weeks of intravenous antibiotics with concurrent angiotensin receptor blockade, his kidney function recovered with improvement in hypocomplementemia and proteinuria. This case report highlights the early recognition and comprehensive evaluation of a rare organism causing IE-associated GN, which allowed for renal recovery and preserved cardiac function

Assessment of kidney function in preterm infants: lifelong implications

This educational review will highlight the historical and contemporary references that establish a basic understanding of measurements of kidney function in the neonate and its relevance for the life of an individual. Importantly, the differential renal function of preterm infants relative to term infants has become paramount with the increased viability of preterm infants and the realization that kidney function is associated with gestational age. Moreover, neonatal kidney function is primarily associated with absolute renal mass and hemodynamic stability. Neonatal kidney function and its early developmental progression predict lifelong cardiovascular and renal disease risks. Validation of estimation equations of kidney function in this population has provided important reference data for other investigations and a clinical basis for prospective and longitudinal follow-up. Future research should be directed towards a better understanding of surrogate markers of kidney function from infancy through adulthood. Pediatric nephrologists should be aware of the developmental aspects of kidney function including the importance of the congenital nephron endowment and the preservation of kidney function throughout a lifetime.• Nephrogenesis occurs in utero in concert with other organ systems by branching morphogenesis, including the lungs, pancreas, and vascular tree, with over 60 % of nephrons being formed during the last trimester.• Infants born preterm before 36 weeks’ gestation are in active nephrogenesis and are at increased risk of having a decreased nephron endowment from prenatal and postnatal genetic and epigenetic hazards that will impact the patient for a lifetime.• Post-natal adaptation of kidney function is directly proportional to the number of perfused nephrons, estimated by total kidney volume (TKV), mean arterial pressure (MAP), and gestational age.• Accurate measurement of glomerular filtration rate (GFR) in infants is problematic due to the unavailability of the gold standard inulin. The traditional use of creatinine to estimate GFR is unreliable in preterm infants due to its tubular reabsorption by immature kidneys and its dependence on muscle mass as an endogenous marker. Alternative endogenous markers to estimate GFR are cystatin C and beta trace protein (BTP).• Long-term follow-up of renal function in those born preterm should be life long and should include assessment of GFR, total kidney volume (TKV) relative to body surface area (BSA), and cardiovascular risks including hypertension and vascular stiffness

Applied Metabolomics and Emerging Biomarkers in Neonatal Acute Kidney Injury

Acute kidney injury (AKI) in neonates presents a unique and ongoing challenge in the early diagnosis and subsequent management of these most vulnerable patients. The globally accepted traditional renal functional marker, serum creatinine (SCr), has long been recognized as unreliable in the neonate, particularly in those born preterm and of low birth weight [1]. In the immediate post-natal week, physiologic adjustments in systemic and renal perfusion lead to an increase in glomerular filtration rate (GFR) from as low as 20 ml/min/1.73 m2 to as high as 60 ml/min/1.73 m2 in term infants [1, 2]. Full maturation of GFR will not be achieved until about 2 years of age. Accordingly, the SCr is initially elevated due to the burden of excreting maternal creatinine. This accounts for a pattern of the SCr rising shortly after birth with a subsequent fall to a nadir <0.4 mg/dL (35 μM/L) in infants with normal post-natal renal development. In contrast, infants born preterm are more likely to have a decreased number of nephrons relative to their shortened gestation as well as intrauterine and perinatal stressors which impede a smooth and positive improvement in GFR [1, 2]. Hence, SCr may be inordinately elevated with a delay in decline to an appropriate nadir. A “true” measure of GFR or recognition of any degree of early kidney injury has been elusive in this setting [2]. While continuing to refine SCr-based definitions of neonatal AKI, a few pioneers have focused research efforts in the emerging field of “omics” in systems biology [3–5]. The suffix, “omics” emerged at the turn of the century to designate a field of biology devoted to the use of high throughput technologies to characterize the molecules that define the structure and function of an organism [5, 6]. Hence, the terms “genomics,” “proteomics,” “metabolomics” and others can be applied to better understand the pathophysiology and to develop biomarkers for the early diagnosis and treatment of neonatal AKI (Fig. 16.1)

Cardio-renal consequences of low birth weight and preterm birth

In this comprehensive review of cardio-renal syndrome in preterm, low birth weight infants, we present contemporary evidence for alterations in nephrogenesis and vasculogenesis among this vulnerable population. There is substantial evidence that the nephron endowment, the number of nephrons that an individual is allotted for a lifetime, is determined by the length of gestation, the intra-uterine environment and the brief, but significant, postnatal course. Since nephrogenesis is complete by 36weeks' gestation in utero, preterm birth during active nephrogenesis predisposes to an abrupt cessation in development leading to a reduced nephron endowment. In addition, other organ systems are simultaneously developing by “branching morphogenesis” including the lungs, vascular tree and endocrine organs such as the pancreas. Importantly, elastin, the scleroprotein that imparts elasticity to the vascular tree, is laid down during angiogenesis in utero and its production after birth is negligible. Instead, elastin is replaced by collagen and fibrosis with aging imparting stiffness to the macro-vessels. Moreover, the micro-vessels (capillaries) are similarly affected with a decreased density, termed rarefaction, in vital organ tissues leading to retinopathy and insulin resistance. This developmental synergism predisposes to concordant abnormalities in endovascular function, nephropenia, hyperfiltration, vascular stiffness and simultaneous cardio-renal disease throughout a lifespan. The longevity of preterm-born adults has been substantially abbreviated by these structural and functional alterations in organ systems. It is essential to recognize early indicators of cardio-renal syndrome and to provide early life-style and pharmacological interventions directed towards preserving vascular and renal function throughout a lifetime with the goal to promote longevity and quality of life

Donor considerations in pediatric kidney transplantation

This article reviews kidney transplant donor options for children with end-stage kidney disease (ESKD). Global access to kidney transplantation is variable. Well-established national policies, organizations for organ procurement and allocation, and donor management policies may account for higher deceased donor (DD transplants) in some countries. Living donor kidney transplantation (LD) predominates in countries where organ donation has limited national priority. In addition, social, cultural, religious and medical factors play a major role in both LD and DD kidney transplant donation. Most children with ESKD receive adult-sized kidneys. The transplanted kidney has a finite survival and the expectation is that children who require renal replacement therapy from early childhood will probably have 2 or 3 kidney transplants in their lifetime. LD transplant provides better long-term graft survival and is a better option for children. When a living related donor is incompatible with the intended recipient, paired kidney exchange with a compatible unrelated donor may be considered. When the choice is a DD kidney, the decision-making process in accepting a donor offer requires careful consideration of donor history, kidney donor profile index, HLA matching, cold ischemia time, and recipient's time on the waiting list. Accepting or declining a DD offer in a timely manner can be challenging when there are undesirable facts in the donor's history which need to be balanced against prolonging dialysis in a child. An ongoing global challenge is the significant gap between organ supply and demand, which has increased the need to improve organ preservation techniques and awareness for organ donation

A Pediatric Case of Sirolimus-Associated Pneumonitis After Kidney Transplantation

Sirolimus is an immunosuppressive medication often used in solid organ transplantation. It has been associated with severe side effects, including pulmonary toxicity. In adult patients, a single center study found that 14% of those treated with sirolimus developed pulmonary pneumonitis; however, the incidence in the pediatric population is not known. Most reports in adult patients indicate that elevated drug concentrations and a prolonged duration of use are associated with pulmonary toxicity. We report a case of a 17-year-old male kidney transplant recipient who developed rapid-onset respiratory failure, necessitating mechanical ventilation and acute renal replacement therapy for ultrafiltration secondary to sirolimus-induced pneumonitis. He had been treated for acute rejection with corticosteroids 17 days prior to the development of pneumonitis. His symptoms developed within 1 week of initiation of sirolimus and with a serum concentration of 1.1 ng/mL. Sirolimus was discontinued, and, following aggressive diuresis and ventilatory support, his respiratory status returned to baseline. Sirolimus-induced pneumonitis is an important diagnosis to be considered in any transplant recipient receiving sirolimus with new onset fever, cough, or dyspnea without an identifiable source, especially if there is a preceding history of treatment with high-dose corticosteroids