Minimal change disease accounts for 70% to 90% of cases of nephrotic syndrome in children. It also causes nephrotic syndrome in adults, including patients older than age 60. Renal function is altered ...moderately in approximately 20% to 30% of patients because foot-process fusion impairs filtration of water and solutes. The glomerular filtration rate is reduced by approximately 20% to 30% and returns to baseline with remission of proteinuria. Over the past 50 years, a number of publications have reported cases of acute kidney injury occurring in approximately one-fifth to one-third of adult cases in the absence of prior or concomitant renal disease. Clinical attributes point to a male predominance, age >50, massive proteinuria, severe hypoalbuminemia, a background of hypertension and vascular lesions on kidney biopsy, along with ischemic tubular necrosis. Acute kidney injury may require dialysis for weeks or months until remission of proteinuria allows resolution of oliguria. In some cases, renal function does not recover. An effect of endothelin-1–induced vasoconstriction at the onset of proteinuria has been proposed to explain tubular cell ischemic necrosis. The main factors causing acute kidney injury in patients with minimal change disease are diuretic-induced hypovolemia and nephrotoxic agents. Acute kidney injury is uncommon in children in the absence of intercurrent complications. Infection, nephrotoxic medication, and steroid resistance represent the main risk factors. In all patients, the goal of supportive therapy is essentially to buy time until glucocorticoids obtain remission of proteinuria, which allows resolution of renal failure.
BSA ingested in food can escape the intestinal barrier and induce antibovine serum albumin antibodies. The authors of this study identified circulating BSA in patients with membranous nephropathy and ...in immune deposits in four children.
Membranous nephropathy is the most common cause of the nephrotic syndrome in adults but is rare in children.
1
,
2
The central pathogenesis involves the formation of subepithelial immune deposits that are responsible for functional impairment of the glomerular capillary wall.
1
,
3
Two major antigens have been identified. The first is neutral endopeptidase, the alloantigen involved in neonatal cases of membranous nephropathy,
4
and the second is the M-type phospholipase A
2
receptor (PLA
2
R), which has been identified in idiopathic membranous nephropathy.
5
Idiopathic membranous nephropathy is considered an autoimmune disease, whereas secondary forms involve exogenous antigens such as viral, bacterial, . . .
Atypical hemolytic uremic syndrome (aHUS) is a rare complement-mediated kidney disease that was first recognized in children but also affects adults. This study assessed the disease presentation and ...outcome in a nationwide cohort of patients with aHUS according to the age at onset and the underlying complement abnormalities.
A total of 214 patients with aHUS were enrolled between 2000 and 2008 and screened for mutations in the six susceptibility factors for aHUS and for anti-factor H antibodies.
Onset of aHUS occurred as frequently during adulthood (58.4%) as during childhood (41.6%). The percentages of patients who developed the disease were 23%, 40%, 70%, and 98% by age 2, 18, 40, and 60 years, respectively. Mortality was higher in children than in adults (6.7% versus 0.8% at 1 year) (P=0.02), but progression to ESRD after the first aHUS episode was more frequent in adults (46% versus 16%; P<0.001). Sixty-one percent of patients had mutations in their complement genes. The renal outcome was not significantly different in adults regardless of genetic background. Only membrane cofactor protein (MCP) and undetermined aHUS were less severe in children than adults. The frequency of relapse after 1 year was 92% in children with MCP-associated HUS and approximately 30% in all other subgroups.
Mortality rate was higher in children than adults with aHUS, but renal prognosis was worse in adults than children. In children, the prognosis strongly depends on the genetic background.
Autosomal dominant polycystic kidney disease (ADPKD) caused by mutations in PKD1 is significantly more severe than PKD2. Typically, ADPKD presents in adulthood but is rarely diagnosed in utero with ...enlarged, echogenic kidneys. Somatic mutations are thought crucial for cyst development, but gene dosage is also important since animal models with hypomorphic alleles develop cysts, but are viable as homozygotes. We screened for mutations in PKD1 and PKD2 in two consanguineous families and found PKD1 missense variants predicted to be pathogenic. In one family, two siblings homozygous for R3277C developed end stage renal disease at ages 75 and 62 years, while six heterozygotes had few cysts. In the other family, the father and two children with moderate to severe disease were homozygous for N3188S. In both families homozygous disease was associated with small cysts of relatively uniform size while marked cyst heterogeneity is typical of ADPKD. In another family, one patient diagnosed in childhood was found to be a compound heterozygote for the PKD1 variants R3105W and R2765C. All three families had evidence of developmental defects of the collecting system. Three additional ADPKD families with in utero onset had a truncating mutation in trans with either R3277C or R2765C. These cases suggest the presence of incompletely penetrant PKD1 alleles. The alleles alone may result in mild cystic disease; two such alleles cause typical to severe disease; and, in combination with an inactivating allele, are associated with early onset disease. Our study indicates that the dosage of functional PKD1 protein may be critical for cyst initiation.
Eculizumab in Severe Shiga-Toxin–Associated HUS Fremeaux-Bacchi, Véronique; Boppel, Tobias; Oualha, Mehdi ...
The New England journal of medicine,
06/2011, Letnik:
364, Številka:
26
Journal Article
Recenzirano
This letter reports treatment of three children with severe, dialysis-requiring Shiga-toxin–induced hemolytic–uremic syndrome (HUS) with eculizumab, a monoclonal anti-C5 antibody. The condition of ...all three children improved rapidly.
To the Editor:
The hemolytic–uremic syndrome (HUS), a thrombotic microangiopathy, most commonly occurs secondary to infection with Shiga-toxin–producing
Escherichia coli
(STEC-HUS), although rare, atypical forms are associated with abnormalities in complement-regulating proteins. The inhibition of terminal complement complex formation by the monoclonal C5 antibody eculizumab has recently been reported as a treatment for atypical HUS.
1
We report on three 3-year-old patients with severe STEC-HUS that required hemodialysis. In Patient 1, plasma exchanges were performed because of low C3 and elevated C3d serum concentrations, which suggested complement activation. Plasma exchange was also performed in Patient 2 because of severe central nervous . . .
Nephronophthisis (NPH) is an autosomal recessive disease characterized by a chronic tubulointerstitial nephritis that progress to terminal renal failure during the second decade (juvenile form) or ...before the age of 5 years (infantile form). In the juvenile form, a urine concentration defect starts during the first decade, and a progressive deterioration of renal function is observed in the following years. Kidney size may be normal, but loss of corticomedullary differentiation is often observed, and cysts occur usually after patients have progressed to end-stage renal failure. Histologic lesions are characterized by tubular basement membrane anomalies, tubular atrophy, and interstitial fibrosis. The infantile form is characterized by cortical microcysts and progression to end-stage renal failure before 5 years of age. Some children present with extrarenal symptoms: retinitis pigmentosa (Senior-Løken syndrome), mental retardation, cerebellar ataxia, bone anomalies, or liver fibrosis. Positional cloning and candidate gene approaches led to the identification of eight causative genes (
NPHP1, 3, 4, 5, 6, 7, 8,
and
9
) responsible for the juvenile NPH and one gene
NPHP2
for the infantile form. NPH and associated disorders are considered as ciliopathies, as all
NPHP
gene products are expressed in the primary cilia, similarly to the polycystic kidney disease (PKD) proteins.
Nephropathic cystinosis is a multisystem autosomal recessive disease caused by cystine accumulation, which is usually treated by oral cysteamine. In order to determine long-term effects of this ...therapy, we enrolled 86 adult patients (mean age 26.7 years) diagnosed with nephropathic cystinosis, 75 of whom received cysteamine. Therapy was initiated at a mean age of 9.9 years with a mean duration of 17.4 years. By last follow-up, 78 patients had end-stage renal disease (mean age 11.1 years), 62 had hypothyroidism (mean age 13.4), 48 developed diabetes (mean age 17.1 years), and 32 had neuromuscular disorders (mean age 23.3 years). Initiating cysteamine therapy before 5 years of age significantly decreased the incidence and delayed the onset of end-stage renal disease, and significantly delayed the onset of hypothyroidism, diabetes, and neuromuscular disorders. The development of diabetes and hypothyroidism was still significantly delayed, however, in patients in whom therapy was initiated after 5 years of age, compared with untreated patients. The life expectancy was significantly improved in cysteamine-treated versus untreated patients. Thus, cysteamine decreases and delays the onset of complications and improves life expectancy in cystinosis. Hence, cysteamine therapy should be introduced as early as possible during childhood and maintained lifelong.
Alport syndrome inevitably leads to end-stage renal disease and there are no therapies known to improve outcome. Here we determined whether angiotensin-converting enzyme inhibitors can delay time to ...dialysis and improve life expectancy in three generations of Alport families. Patients were categorized by renal function at the initiation of therapy and included 33 with hematuria or microalbuminuria, 115 with proteinuria, 26 with impaired renal function, and 109 untreated relatives. Patients were followed for a period whose mean duration exceeded two decades. Untreated relatives started dialysis at a median age of 22 years. Treatment of those with impaired renal function significantly delayed dialysis to a median age of 25, while treatment of those with proteinuria delayed dialysis to a median age of 40. Significantly, no patient with hematuria or microalbuminuria advanced to renal failure so far. Sibling pairs confirmed these results, showing that earlier therapy in younger patients significantly delayed dialysis by 13 years compared to later or no therapy in older siblings. Therapy significantly improved life expectancy beyond the median age of 55 years of the no-treatment cohort. Thus, Alport syndrome is treatable with angiotensin-converting enzyme inhibition to delay renal failure and therapy improves life expectancy in a time-dependent manner. This supports the need for early diagnosis and early nephroprotective therapy in oligosymptomatic patients.
Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of ESRD in children, but the proportion of patients with individual CAKUT entities progressing to ESRD during ...adulthood and their long-term clinical outcomes are unknown. This study assessed the age at onset of renal replacement therapy (RRT) and patient and renal graft survival in patients with CAKUT across the entire age range.
Patients with CAKUT were compared with age-matched patients who were undergoing RRT for other renal disorders on the basis of data from the European Renal Association-European Dialysis and Transplant Association Registry. Competing risk and Cox regression analyses were conducted.
Of 212,930 patients commencing RRT from 1990 to 2009, 4765 (2.2%) had renal diagnoses consistent with CAKUT. The proportion of incident RRT patients with CAKUT decreased from infancy to childhood and then increased until age 15-19 years, followed by a gradual decline throughout adulthood. Median age at RRT start was 31 years in the CAKUT cohort and 61 years in the non-CAKUT cohort (P<0.001). RRT was started earlier (median, 16 years) in patients with isolated renal dysplasia than in those with renal hypoplasia and associated urinary tract disorders (median, 29.5-39.5 years). Patients with CAKUT survived longer than age- and sex-matched non-CAKUT controls because of lower cardiovascular mortality (10-year survival rate, 76.4% versus 70.7%; P<0.001).
CAKUT leads to ESRD more often at adult than pediatric age. Treatment outcomes differ from those of acquired kidney diseases and vary within CAKUT subcategories.
Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative ...pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody. We found that this form of aHUS primarily affects children between 9 and 13 years old but it also affects adults. It presents with a high frequency of gastrointestinal symptoms and with extrarenal complications and has a relapsing course. Activation of the alternative pathway of complement at the onset of disease portends a poor prognosis. Early specific treatment may lead to favorable outcomes. These data should improve the recognition and diagnosis of this form of aHUS and help identify patients at high risk of a poor outcome.
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