Pediatric nephrology

Renal microvascular lesions, common in lupus nephritis (LN), are associated with long-term poor outcomes. There are mainly five pathological types of renal microvascular lesions in LN: (1) vascular immune complex deposits (ICD), (2) arteriosclerosis (AS), (3) thrombotic microangiopathy (TMA), (4) non-inflammatory necrotizing vasculopathy (NNV), and (5) true renal vasculitis (TRV). The pathogenesis of renal microvascular lesions in LN remains to be elucidated. The activation and dysfunction of endothelial cells, in addition to the contribution of immune system dysfunction, especially the immune complex-induced vascular inflammation and antiphospholipid antibody-associated thrombotic events, are key mechanisms in the development of vascular lesions in LN that need to be further investigated...

Transplant-associated thrombotic microangiopathy (TA-TMA) is one of the early endothelial complications post Hematopoietic Stem Cell Transplant (HSCT). Several mechanisms during HSCT can contribute to systemic capillary endothelial damage which can lead to TA-TMA among other complications as capillary leak syndrome or engraftment syndrome. Early diagnosis of TA-TMA contributes a challenge due to overlapping clinical manifestations and the absence of specific diagnostic criteria. Incidence is greatly variable between 1-76% according to risk factors of patients and the definition used to confirm the diagnosis...

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endothelial damage syndrome that is increasingly identified as a complication of both autologous and allogeneic hematopoietic cell transplantation (HCT) in children. If not promptly diagnosed and treated, TA-TMA can lead to significant morbidity (e.g., permanent renal injury) or mortality. However, as the recognition of the early stages of TA-TMA may be difficult, we propose a TA-TMA "triad" of hypertension, thrombocytopenia (or platelet transfusion refractoriness), and elevated lactate dehydrogenase (LDH)...

BACKGROUND: The kidneys play an important role in phosphate homeostasis. Patients with CKD develop hyperphosphatemia in the later stages of the disease. Currently, treatment options are limited to dietary phosphate restriction and oral phosphate binders. The sodium-phosphate cotransporter Npt2a, which mediates a large proportion of phosphate reabsorption in the kidney, might be a good therapeutic target for new medications for hyperphosphatemia. METHODS: The authors assessed the effects of the first orally bioavailable Npt2a inhibitor (Npt2a-I) PF-06869206 in normal mice and mice that had undergone subtotal nephrectomy (5/6 Nx), a mouse model of CKD...

Bartter and Gitelman syndromes are rare inherited tubulopathies characterized by hypokalaemic, hypochloraemic metabolic alkalosis. They are caused by mutations in at least 7 genes involved in the reabsorption of sodium in the thick ascending limb (TAL) of the loop of Henle and/or the distal convoluted tubule (DCT). Different subtypes can be distinguished and various classifications have been proposed based on clinical symptoms and/or the underlying genetic cause. Yet, the clinical phenotype can show remarkable variability, leading to potential divergences between classifications...

Congenital anomalies of the kidneys or lower urinary tract (CAKUT) are the most common causes of renal failure in children and account for 25% of end-stage renal disease in adults. The spectrum of anomalies includes renal agenesis; hypoplasia; dysplasia; supernumerary, ectopic or fused kidneys; duplication; ureteropelvic junction obstruction; primary megaureter or ureterovesical junction obstruction; vesicoureteral reflux; ureterocele; and posterior urethral valves. CAKUT originates from developmental defects and can occur in isolation or as part of other syndromes...

Renal ciliopathies are a group of disorders characterised by nephronophthisis, cystic kidneys or renal cystic dysplasia whose underlying disease pathogenesis is related to abnormal structure or function of the primary cilia complex. The number of renal ciliopathies continues to expand as genomic and genetic approaches identify novel causes. This in turn provides new opportunities to explore disease mechanisms and therapeutic approaches to target cystic kidney disease and other associated phenotypes. Here we review recent advances in the field of renal ciliopathies and how these allow new insights into this fascinating spectrum of diseases...

Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood...

Persistent hypokalemic hypochloremic metabolic alkalosis represents a heterogeneous group of genetic disorders of which the most common is Bartter syndrome (BS). BS is an inherited renal tubulopathy caused by defective salt reabsorption in the thick ascending loop of Henle, which results in persistent hypokalemic hypochloremic metabolic alkalosis. Here we report a 10-year-old girl of a consanguineous family. She presented prenatally with severe polyhydramnios and distended bowel loops. Thereafter, she displayed failure to thrive and had recurrent admissions due to dehydration episodes associated with diarrhea, and characterized by hypokalemia, hypochloremia and metabolic alkalosis...

RATIONALE: Bartter syndrome is an autosomal-recessive inherited disease in which patients present with hypokalemia and metabolic alkalosis. We present 1 case with Bartter syndrome, due to a novel compound heterozygous mutation in the KCNJ1 gene encoding the ATP-sensitive inward rectifier potassium channel in the thick ascending limb of the loop of Henle. PATIENT CONCERNS: A patient was admitted to our hospital because of weakness, polyuria, and polydipsia. At presentation to our hospital, the female Chinese patient was 34 years old and her physical examination was normal...

The aetiology of Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, characterized by uterovaginal agenesis in 46,XX women, remains poorly understood. Since familial occurrences are rare, genetic findings reported so far only apply to a minority of mainly sporadic cases and most studies have not included other family members enabling segregation analysis. Herein, we report on the investigation of a unique three-generation family of two female cousins with MRKH syndrome and unilateral renal agenesis (RA) and two deceased male relatives with RA...

Immunoglobulin A nephropathy (IgAN) is the most frequent glomerular disease worldwide and a leading cause of end-stage renal disease. Particularly challenging to the clinician is the early identification of patients at high risk of progression, an estimation of the decline in renal function, and the selection of only those that would benefit from additional immunosuppressive therapies. Nevertheless, the pathway to a better prognostication and to the development of targeted therapies in IgAN has been paved by recent understanding of the genetic and molecular basis of this disease...

INTRODUCTION: Dent's disease is a rare X-linked recessive disorder that manifests in childhood or early adulthood and can lead to end-stage renal disease (ESRD). It occurs in males, who are hemizygous. In patients who develop ESRD, a deceased donor kidney transplant cures the disease. Females are obligate carriers of the mutated gene, and some show a mild Dent's disease phenotype. There may be reason for concern when considering a female obligate carrier (i.e., the mother) for kidney donation because of the risk of kidney function deterioration...

BACKGROUND: Recurrence of focal segmental glomerulosclerosis (FSGS) in renal allograft recipients after first transplant occurs in the second graft in virtually all patients. There is little evidence regarding optimal treatment. CASE PRESENTATION: A 55-year-old man with primary FSGS and disease recurrence in both the first and the second kidney grafts is presented. In 1999, the patient developed FSGS 3 years after transplant, which was treated with plasmapheresis and cyclophosphamide...

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is still one of the common causes of refractory nephrotic syndrome. Nephrin, encoded by podocyte-specific NPHS1 gene, participated in the pathogenesis of FSGS. The sites of NPHS1 mutations in FSGS is not clarified very well. In this study, we investigated the specific mutations of NPHS1 gene in Chinese patients with sporadic FSGS. METHODS: A total of 309 patients with sporadic FSGS were collected and screened for NPHS1 mutations by second-generation sequencing...

BACKGROUND: Chronic nephrotoxicity with potentially irreversible lesions is a major concern regarding calcineurin inhibitor (CNI) treatment in children with severe forms of idiopathic nephrotic syndrome (INS). CASE-DIAGNOSIS/TREATMENT: We retrospectively included all children on CNI for steroid-dependent INS with a duration of CNI treatment of more than 1 year. Only patients in whom CNI could not be replaced by mycophenolate mofetil were included. All included patients underwent a kidney biopsy...

Focal segmental glomerulosclerosis (FSGS) accounts for about 40% of all nephrotic syndrome cases in adults. The presence of several potential circulating factors has been suggested in patients with primary FSGS and particularly in patients with recurrent disease after transplant. Irrespectively of the nature of the circulating factors, this study was aimed at identifying early glomerular/podocyte-specific pathways that are activated by the sera of patients affected by FSGS. Kidney biopsies were obtained from patients undergoing kidney transplantation due to primary FSGS...

BACKGROUND: Treatment with eculizumab in Shiga toxin-associated haemolytic and uraemic syndrome (STEC-HUS) remains controversial despite its increasing utilization. The aim of our study was to evaluate the outcomes of children treated with eculizumab for STEC-HUS in a single-centre matched cohort study. METHODS: Data were retrospectively collected from medical records of children diagnosed with STEC-HUS. The outcomes of patients treated with eculizumab for STEC-HUS were compared with those of a control group of untreated patients matched for age, sex and severity of acute kidney injury with a 1:2 matching scheme...

The complement system is well known for its role in innate immunity and in maintenance of tissue homeostasis, providing a first line of defence against infection and playing a key role in flagging apoptotic cells and debris for disposal. Unfortunately, complement also contributes to pathogenesis of many diseases, in some cases driving pathology, and in others amplifying or exacerbating the inflammatory and damaging impact of non-complement disease triggers. The driving role of complement in a single disease, paroxysmal nocturnal hemoglobinuria (PNH), provoked the development and eventual FDA (US Food and Drug Administration) approval of eculizumab (Soliris™), an anti-C5 antibody, for therapy...

AIMS: BK polyomavirus nephropathy (BKPyVN) is an important cause of allograft failure after renal transplantation. Despite early screening for the virus, allograft loss from BKPyVN is still experienced in up to 14% of all renal transplant recipients. The aim of this study was to investigate the association between BKPyVN histopathologic disease severity and allograft outcome at our center. METHODS: Kidney transplant recipients who had undergone transplantation between 2002 and 2014 with biopsy proven BKPyVN were eligible for this retrospective study...