Prevalence and potential relevance of hyperuricemia in pediatric kidney transplant recipients—a CERTAIN registry analysis

Background: Asymptomatic hyperuricemia is frequently observed in pediatric kidney transplant recipients; symptomatic hyperuricemia, however, is a rare complication. Only few data are available in this patient population. We, therefore, investigated the prevalence of hyperuricemia and its association with kidney transplant function and blood pressure in a multicenter cohort of pediatric kidney transplant recipients. Methods: This is a retrospective, observational multicenter registry study. All pediatric kidney transplant recipients in the CERTAIN database with at least one documented serum uric acid level and a follow-up of 5 years posttransplant were eligible. We identified 151 patients with 395 measurements of serum uric acid. We calculated the prevalence of hyperuricemia, analyzed potential risk factors and clinical consequences such as elevated blood pressure and reduced estimated glomerular filtration rate (eGFR). Statistical analysis was performed using IBM SPSS Statistics 26. Results: One hundred and ten of 395 (27.8%) serum uric acid levels were above 416 µmol/L (7.0 mg/dL), defined as the upper limit of normal. Univariate analysis showed a significant (p = .026) inverse association of serum uric acid with eGFR overtime. There was no significant association of serum uric acid concentrations with body mass index (z-score), blood pressure (z-score), or sex. No episodes of gout were documented. Conclusion: This study shows that hyperuricemia is present in a considerable number of patients sometime after pediatric kidney transplantation and is associated with lower eGFR. Whether hyperuricemia contributes to faster decline of graft function or to the overall cardiovascular risk of these patients remains to be elucidated. Keywords: gout; long-term outcome; pediatric kidney transplantation; uric acid; uric acid-lowering therapy

NPHP4, a cilia-associated protein, negatively regulates the Hippo pathway

The cilia-associated protein NPHP4 is a negative regulator of Hippo signaling that modulates cell proliferation in mammals

Acute kidney failure in preterm infants and neonates

Background: Numerous excellent studies during recent years focused on acute kidney failure in neonates. Objective: This review article gives an overview on the current study situation on acute kidney failure (AKI) in preterm infants and neonates. These findings comprise data on the incidence, risk factors and possible forms of treatment as well as consequences of postnatal acute kidney failure further on in life. Material and methods: A literature search was carried out in PubMed with a special focus on current treatment recommendations and guidelines. Results: As already shown for other age groups, acute kidney failure is also a frequent finding in preterm infants and neonates especially during intensive medical care and is an independent risk factor for increased mortality and longer duration of hospitalization. Risk factors differ between early (within the first 7 days of life) and late acute kidney failure. In addition to avoidance of nephrotoxic medication, the administration of caffeine citrate was identified as an effective protective factor in preterm infants. Discussion: The increasing research activities on acute kidney failure in neonates could not only identify risk factors and protective factors but also increased awareness for this condition. The impact of postnatal acute kidney injury on the risk of a chronic kidney disease during adolescence and adulthood needs to be determined in further long-term studies. In the context of renal programming, prematurity per se as well as other perinatal risk factors have already been shown to substantially increase the risk of chronic kidney disease in later life

Molecular causes of congenital anomalies of the kidney and urinary tract (CAKUT)

Congenital anomalies of the kidney and urinary tract (CAKUT) occur in 0.5-1/100 newborns and as a group they represent the most frequent cause for chronic kidney failure in children. CAKUT comprise clinically heterogeneous conditions, ranging from mild vesicoureteral reflux to kidney aplasia. Most forms of CAKUT share the pathophysiology of an impaired developmental interaction of the ureteric bud (UB) and the metanephric mesenchyme (MM). In most cases, CAKUT present as an isolated condition. They also may occur as a component in rare multi-organ syndromes. Many CAKUT probably have a multifactorial etiology. However, up to 20% of human patients and > 200 transgenic mouse models have a monogenic form of CAKUT, which has fueled our efforts to unravel molecular kidney (mal-)development. To date, genetic variants in more than 50 genes have been associated with (isolated) CAKUT in humans. In this short review, we will summarize typical imaging findings in patients with CAKUT and highlight recent mechanistic insight in the molecular pathogenesis of monogenic forms of CAKUT

Complement activation in children with Streptococcus pneumoniae associated hemolytic uremic syndrome

Background Hemolytic uremic syndrome caused by invasive pneumococcal disease (P-HUS) is rare in children and adolescents, but accompanied by high mortality in the acute phase and complicated by long-term renal sequelae. Abnormalities in the alternative complement pathway may additionally be contributing to the course of the disease but also to putative treatment options. Methods Retrospective study to assess clinical course and laboratory data of the acute phase and outcome of children with P-HUS. Results We report on seven children (median age 12 months, range 3-28 months) diagnosed with P-HUS. Primary organ manifestation was meningitis in four and pneumonia in three patients. All patients required dialysis which could be discontinued in five of them after a median of 25 days. In two patients, broad functional and genetic complement analysis was performed and revealed alternative pathway activation and risk haplotypes in both. Three patients were treated with the complement C5 inhibitor eculizumab. During a median follow-up time of 11.3 years, one patient died due to infectious complications after transplantation. Two patients showed no signs of renal sequelae. Conclusions Although pathophysiology in P-HUS remains as yet incompletely understood, disordered complement regulation seems to provide a clue to additional insights for pathology, diagnosis, and even targeted treatment