Intraflagellar transport (IFT) depends on two evolutionarily conserved modules, subcomplexes A (IFT-A) and B (IFT-B), to drive ciliary assembly and maintenance. All six IFT-A components and their motor protein, DYNC2H1, have been linked to human skeletal ciliopathies, including asphyxiating thoracic dystrophy (ATD; also known as Jeune syndrome), Sensenbrenner syndrome, and Mainzer-Saldino syndrome (MZSDS). Conversely, the 14 subunits in the IFT-B module, with the exception of IFT80, have unknown roles in human disease. To identify additional IFT-B components defective in ciliopathies, we independently performed different mutation analyses: candidate-based sequencing of all IFT-B-encoding genes in 1,467 individuals with a nephronophthisis-related ciliopathy or whole-exome resequencing in 63 individuals with ATD. We thereby detected biallelic mutations in the IFT-B-encoding gene IFT172 in 12 families. All affected individuals displayed abnormalities of the thorax and/or long bones, as well as renal, hepatic, or retinal involvement, consistent with the diagnosis of ATD or MZSDS. Additionally, cerebellar aplasia or hypoplasia characteristic of Joubert syndrome was present in 2 out of 12 families. Fibroblasts from affected individuals showed disturbed ciliary composition, suggesting alteration of ciliary transport and signaling. Knockdown of ift172 in zebrafish recapitulated the human phenotype and demonstrated a genetic interaction between ift172 and ift80. In summary, we have identified defects in IFT172 as a cause of complex ATD and MZSDS. Our findings link the group of skeletal ciliopathies to an additional IFT-B component, IFT172, similar to what has been shown for IFT-A.

Henoch-Schönlein purpura is the most common systemic vasculitis of childhood. In the majority of children, the outcome of Henoch-Schönlein purpura is excellent with spontaneous resolution of symptoms and signs. However, a small subset of patients will develop long-term sequelae in the form of chronic kidney disease. While the clinical presentation and diagnosis of Henoch-Schönlein purpura is straightforward, treatment of Henoch-Schönlein purpura nephritis and long-term renal outcomes of more severely affected children are less certain. This review article gives a general overview of Henoch-Schönlein purpura with emphasis on recently published information, including the new classification of childhood vasculitis, insights into pathogenesis of Henoch-Schönlein purpura and a summary of various treatments of established Henoch-Schönlein purpura nephritis.

Despite the increasing diagnostic rate of genomic sequencing, the genetic basis of more than 50% of heritable kidney disease remains unresolved. Kidney organoids differentiated from induced pluripotent stem cells (iPSCs) of individuals affected by inherited renal disease represent a potential, but unvalidated, platform for the functional validation of novel gene variants and investigation of underlying pathogenetic mechanisms. In this study, trio whole-exome sequencing of a prospectively identified nephronophthisis (NPHP) proband and her parents identified compound-heterozygous variants in IFT140, a gene previously associated with NPHP-related ciliopathies. IFT140 plays a key role in retrograde intraflagellar transport, but the precise downstream cellular mechanisms responsible for disease presentation remain unknown. A one-step reprogramming and gene-editing protocol was used to derive both uncorrected proband iPSCs and isogenic gene-corrected iPSCs, which were differentiated to kidney organoids. Proband organoid tubules demonstrated shortened, club-shaped primary cilia, whereas gene correction rescued this phenotype. Differential expression analysis of epithelial cells isolated from organoids suggested downregulation of genes associated with apicobasal polarity, cell-cell junctions, and dynein motor assembly in proband epithelial cells. Matrigel cyst cultures confirmed a polarization defect in proband versus gene-corrected renal epithelium. As such, this study represents a "proof of concept" for using proband-derived iPSCs to model renal disease and illustrates dysfunctional cellular pathways beyond the primary cilium in the setting of IFT140 mutations, which are established for other NPHP genotypes.

FSGS recurrence after kidney transplantation was more common in live donor kidneys. Despite this, graft survival in live donor recipients was significantly better for both children and adults with FSGS. We propose that live donor transplantation should not be avoided in patients with FSGS.

Long term follow-up from this large dRTA cohort shows an overall favourable outcome with normal adult height for most and no patient with CKD 5. Yet, 82% of adult patients have CKD 2-4. Importance of adequate metabolic control was highlighted by better growth and renal function but was achieved in only half of patients.

Specialist assessment and management is required for children who are considered at high risk of serious illness (underlying structural urinary tract abnormalities or neurogenic bladder or kidney transplant recipients). These children are beyond the scope of these guidelines, and it is important that they are excluded from the recommendations detailed below. DIAGNOSIS Guideline recommendationsa. We recommend that the diagnosis of urinary tract infection (UTI) only be made on the basis of clinical symptoms (see below) in association with a positive urine culture. (1B) b. We suggest that the presence of bacteriuria (by microscopy with gram stain) on an appropriately collected urine specimen can be used as the basis for a presumptive diagnosis of UTI. (2B) c. We recommend that culture of an appropriately collected urine specimen (see below) is required for definitive diagnosis of UTI (1B) and that UTI diagnosis not be made solely on the basis of:• Urinary dipstick testing for leucocyte esterase or nitrite (1B) or Urine collection e. Suprapubic aspirate (SPA) is the most definitive method of urine culture but is regarded as more invasive than other methods. We recommend the use of clean catch urine (CCU), mid-stream urine (MSU) or in-out catheter specimen urine (CSU) as satisfactory alternate methods for urine collection. (1B) f. If positive urine culture by bag urine is obtained, we recommend it is confirmed on repeat urine culture by SPA, CSU, CCU or MSU. (1B) g. We suggest that SPA collection follow a protocol that ensures a full bladder prior to the procedure. This may involve either clinical assessment of good hydration and delay after voiding by 1 hour or use of bladder ultrasound or both. (2B) Urine culture h. We recommend the following minimum counts of colony forming units (CFU) grown on urine culture be considered as diagnostic of UTI (1B):• SPA: any growth • Bag/pad/cotton ball: not recommended for definitive culture. i. We suggest that the following be taken as indicators of possible contamination (2C):• Any growth from a bag specimen • Growth of more than one organism from any method of urine collection• Growth of skin commensals • CFU counts less than the recommended minimum counts. j. If contamination is possible on initial urine culture, we suggest repeat urine culture if any of the following conditions apply (2C):• Convincing urinary symptoms are present.• The child has a structurally abnormal urinary tract.• There is a history of complicated UTIs. Ungraded suggestions for clinical carea. UTI is more likely in girls and uncircumcised boys (especially between 3 and 6 months), infants <12 months, and if a fever has been present for >2 days and there is an absence of another source of fever on examination. No factor can predict with 100% accuracy the absence of serious bacterial illness in febrile infants <3 months. (ungraded) b. In children with culture-proven UTI, a serum procalcitonin value >0.5 ng/mL predicts reasonably well the presence of renal parenchymal injury, as evidenced by early dimercapto...

Ciliary disorders share typical features, such as polydactyly, renal and biliary cystic dysplasia, and retinitis pigmentosa, which often overlap across diagnostic entities. We report on two siblings of consanguineous parents and two unrelated children, both of unrelated parents, with co-occurrence of Joubert syndrome and Jeune asphyxiating thoracic dystrophy, an association that adds to the observation of common final patterns of malformations in ciliary disorders. Using homozygosity mapping in the siblings, we were able to exclude all known genes/loci for both syndromes except for INVS, AHI1, and three genes from the previously described Jeune locus at 15q13. No pathogenic variants were found in these genes by direct sequencing. In the third child reported, sequencing of RPGRIP1L, ARL13B, AHI1, TMEM67, OFD1, CC2D2A, and deletion analysis of NPHP1 showed no mutations. Although this study failed to identify a mutation in the patients tested, the co-occurrence of Joubert and Jeune syndromes is likely to represent a distinct entity caused by mutations in a yet to be discovered gene. The mechanisms by which certain organ systems are affected more than others in the spectrum of ciliary diseases remain largely unknown.

Reninoma (juxtaglomerular cell tumor) is a rare cause of renin-mediated hypertension. Reninomas are usually diagnosed in adolescents and young adults with occasional reports in younger children. Patients typically present with a long history of headaches leading to a diagnosis of severe hypertension that responds well to antihypertensive treatment targeting the renin-angiotensin-aldosterone system. The clue to clinical diagnosis is the presence of hypokalemia and metabolic alkalosis on the first blood sample drawn before any treatment is instituted. Elevated blood levels of renin and aldosterone confirm the clinical suspicion of renin-mediated hypertension. Diagnostic imaging is employed to identify the source of excessive renin production. While renal ultrasound can miss reninoma, contrast CT or magnetic resonance imaging of the kidneys are diagnostic modalities of choice leading to the correct diagnosis. Renal vein renin sampling with lateralization might help to identify the site of excessive renin production. Nephron-sparing surgery is curative with maintenance of normal blood pressure after discontinuation of antihypertensive medications in the majority of patients. In this paper, we present the case of reninoma in an adolescent girl emphasizing clinical presentation, diagnostic evaluation, and medical and surgical treatment of this rare tumor. We also discuss important points in the management of children presenting with renin-mediated hypertension.