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Journal: Pediatric nephrology (Berlin, Germany)


Can renal prognosis and life expectancy be accurately predicted? Increasingly, the answer is yes. The natural history of different forms of renal disease is becoming clearer; the degree of reduction in glomerular filtration rate (GFR) and the magnitude of proteinuria are strong predictors of renal outcome. Actuarial data on life expectancy from the start of renal replacement therapy are available from renal registries such as the U.S. Renal Data System (USRDS), and the UK Renal Registry. Recently, similar data have become available for patients with chronic kidney disease. Data collected from a large population-based registry in Alberta, Canada and stratified for different levels of estimated GFR (eGFR) have shown that the reduction in life expectancy with kidney failure is not a uremic event associated with starting dialysis but a continuous process that is evident from an eGFR of ≤60 ml/min. Nevertheless, despite the poor prognosis of the last stages of renal failure, progress in the treatment and management of these patients and, in particular, of their cardiovascular risk factors continues to improve long-term outcome.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Dialysis, Renal function


Renovascular hypertension (RVH) can be caused by many different diseases, with the most common being fibromuscular dysplasia (FMD) and Takayasu arteritis (TA). A strikingly different diagnostic pattern is seen in children with RVH from different parts of the world. In Europe and North America, these children are mainly diagnosed as having FMD while in Asia and South Africa they will most often get a diagnosis of TA. When comparing the clinical diagnosis for FMD and TA, it becomes obvious that there is a great deal of overlap between the definitions of these two conditions. Different ways to come to the most accurate diagnosis using imaging of the blood vessel wall and positron emission tomography (PET) will be discussed. How an accurate diagnosis should influence the treatment of the children with these conditions will also be addressed.

Concepts: Diagnosis, Blood vessel, Positron emission tomography, Positron, Europe, Renal artery stenosis, Takayasu's arteritis


BACKGROUND: Posterior urethral valves (PUV) are a common cause of end-stage renal failure in childhood. Our aim was to describe a cohort of patients with PUV and to investigate the predictors of renal impairment. METHODS: We performed a retrospective chart review of children with PUV who were followed at King Abdulaziz University hospital between 2002 and 2011. RESULTS: The cohort comprised 68 boys. There was a significant difference in the duration of follow-up (p = 0.024), nadir serum creatinine (p < 0.001), and last known serum creatinine level (p = 0.001) between the patients with and without renal impairment. The duration of follow-up appeared to be a significant predictor for serum creatinine doubling (p = 0.003; odds ratio, 1.8). There was no difference in the age of presentation, age at the time of the study, and first or last serum creatinine between children who initially had vesicostomy and children who had ablation. CONCLUSIONS: Ablation of PUV or vesicostomy did not influence kidney function in our study cohort. Children with a normal nadir serum creatinine who presented early had a better outcome.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Dialysis, Renal physiology, Creatinine, King Abdulaziz University


Hyponatremia is the most common electrolyte abnormality in clinical practice, but little is known about the association between febrile urinary tract infection (UTI) and hyponatremia or its significance to clinical outcomes.

Concepts: Inflammation, Kidney, Blood, Urinary tract infection, Urine, Infection, Fever


BACKGROUND: Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown. METHODS: A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function. RESULTS: A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible. CONCLUSION: Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.

Concepts: Renal failure, Chronic kidney disease, Kidney, Nephrology, Nephrotic syndrome, Immunosuppressive drug, Nephritic syndrome, Minimal change disease


Blessed were the days when it all made sense and the apparent mechanism for edema formation in nephrotic syndrome was straightforward: the kidneys lost protein in the urine, which lowered the plasma oncotic pressure. Thus, fluid leaked into the interstitium, depleting the intravascular volume with subsequent activation of renin/aldosterone and consequent avid renal sodium retention. As simple as that! Unfortunately, a number of clinical and laboratory observations have raised serious concerns about the accuracy of this “underfill” hypothesis. Instead, an “overfill” hypothesis was generated. Under this assumption, the nephrotic syndrome not only leads to urinary protein wasting, but also to primary sodium retention with consequent intravascular overfilling, with the excess fluid spilling into the flood plains of the interstitium, leading to edema. Recently, an attractive mechanism was proposed to explain this primary sodium retention: proteinuria includes plasma proteinases, such as plasmin, which activate the epithelial sodium channel in the collecting duct, ENaC. In this edition, further evidence for this hypothesis is being presented by confirming increased plasmin content in the urine of children with nephrotic syndrome and demonstrating ENaC activation. If correct, this hypothesis would provide a simple treatment for the edema: pharmacological blockade of ENaC, for instance, with amiloride. Yet, how come clinicians have not empirically discovered the presumed power of ENaC blockers in nephrotic syndrome? And why is it that some patients clearly show evidence of intravascular underfilling? The controversy of over- versus underfilling demonstrates how much we still have to learn about the pathophysiology of nephrotic syndrome.

Concepts: Scientific method, Kidney, Nephrotic syndrome, Ureter, Aldosterone, Edema, Atrial natriuretic peptide, Epithelial sodium channel


Acute kidney injury (AKI) is a commonly encountered complication in critically ill children and portends a worse prognosis. Sepsis-induced AKI (SAKI) is a leading contributor to AKI in children and significantly modifies the risk for less favorable outcome. It has increasingly become clear that SAKI represents a unique and distinct cause of AKI. Studies focused on renal hemodynamics, bioenergetics, and immune-mediated injury have provided further insights into the pathobiology of SAKI; however, many of the nuanced mechanisms remain incompletely understood. Although there have been numerous strategies evaluated for the prevention and management of SAKI, no specific intervention has proven unequivocally efficacious. Currently, the mainstays for managing SAKI focus on alleviating ongoing kidney damage by optimizing systemic and kidney hemodynamic support, avoiding nephrotoxins, and mitigating the anticipated complications of kidney failure. The timely referral for renal support to manage azotemia, metabolic derangements, and fluid accumulation remains critical for this population. The extracorporeal removal of inflammatory mediators has shown some potential benefit in limiting systemic and kidney immune-mediated injury; however, the precise role of these technologies in the management of SAKI has yet to be defined.

Concepts: Inflammation, Renal failure, Chronic kidney disease, Kidney, Nephrology, Acute kidney injury, Management, Fluid mechanics


BACKGROUND: Nephrotic syndrome (NS) is a recognized complication of immune tolerance induction (ITI) therapy, a treatment strategy used to treat inhibitors in patients with hemophilia B receiving factor IX concentrate. CASE DIAGNOSIS/TREATMENT: We present a 4-year-old boy with hemophilia B and an inhibitor who underwent ITI, and developed NS 19 months into this therapy. A percutaneous renal biopsy was safely performed with factor IX (FIX) concentrate administration both preceding and following the procedure. The patient’s inhibitor level had increased to 1.4-1.6 Bethesda Units just prior to the onset of proteinuria. Histology confirmed segmental membranous nephropathy (MGN). The patient was continued on FIX concentrate as ITI and also received 4 weekly doses of rituximab and ongoing immunosuppression with mycophenolate mofetil. This resulted in the complete resolution of his inhibitor and his NS. He continues with a modified ITI regimen and remains inhibitor-free without proteinuria >12 months post-biopsy. CONCLUSIONS: Hemophilia B patients undergoing ITI should be regularly screened for NS. At first detection of proteinuria, with proper precautions, a percutaneous kidney biopsy can be performed safely in patients with low levels of inhibitor. Our patient had segmental MGN with complete remission of NS.

Concepts: Kidney, Patient, Nephrotic syndrome, Proteinuria, Haemophilia B, Mycophenolic acid, Mycophenolate mofetil, Nephritic syndrome


BACKGROUND: Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS). METHODS: This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19 >1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %). RESULTS: Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred. CONCLUSION: The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.

Concepts: Pharmacology, Nephrotic syndrome, Therapy, Pharmacotherapy, Classification of Pharmaco-Therapeutic Referrals, Syndromes, Systemic lupus erythematosus, Nephritic syndrome


Focal segmental glomerulosclerosis (FSGS) is an important cause of glomerular disease in children and adolescents and nearly 50 % of affected patients will progress to end-stage kidney disease over a 5 to 10-year period. Unfortunately, there is no established treatment for disease in the native kidney. Moreover, up to 55 % of patients develop recurrent disease after receiving a kidney transplant, with a substantially higher risk in patients who have already experienced recurrent disease in a prior transplant. A number of clinical and laboratory factors have been identified as risk factors for this complication. In addition, new investigations into podocyte biology and circulating permeability factors have shed light on the cause of recurrent the disease. While a number of novel therapeutic agents have been applied in the management of this problem, there still is no proven treatment. In this review, we summarize recent advances in the epidemiology, pathophysiology, and treatment of recurrent FSGS in pediatric patients who have received a kidney transplant.

Concepts: Chronic kidney disease, Kidney, Nephrology, Medicine, Epidemiology, Organ transplant, Kidney transplantation, Focal segmental glomerulosclerosis