Mutations in Uroplakin IIIA are a rare cause of renal hypodysplasia in humans

BACKGROUND: Renal hypodysplasia, characterized by a decrease in nephron number, small overall kidney size, and maldeveloped renal tissue, is a leading cause of chronic renal failure in young children. Familial clustering and renal hypodysplasia phenotypes observed in transgenic animal models suggest a genetic contribution. Uroplakin IIIa (encoded by UPIIIA) is an integral membrane protein present in urothelial plaques, and the murine UPIIIa knockout is associated with urothelial anomalies and vesicoureteral reflux. De novo UPIIIA mutations recently were identified in 4 of 17 patients with severe bilateral renal adysplasia. METHODS: To evaluate the overall role of UPIIIA in human renal hypodysplasia pathogenesis, we performed UPIIIA mutation analysis in a cohort of 170 pediatric patients affected by severe unilateral or bilateral renal hypodysplasia. Eighty-one patients were affected by bilateral nonobstructive renal hypodysplasia; of these, 61 were without vesicoureteral reflux. Eighty-four patients presented with unilateral nonobstructive renal hypodysplasia, including 24 patients with unilateral multicystic dysplastic kidneys. Family history was positive in 11%. RESULTS: Mutation analysis showed 2 heterozygous mutations not observed in 200 race-matched control chromosomes. In only 1 family was distribution of the UPIIIA mutation consistent with a disease-causing effect. This de novo missense mutation (Gly202Asp) was identified in a patient with unilateral multicystic dysplastic kidneys. The second (intronically located) mutation appeared unlikely to be disease causing because it did not segregate with an obvious disease phenotype in the affected family. CONCLUSION: Our results indicate that de novo mutations in UPIIIA can be involved in defective early kidney development, but probably constitute only a rare cause of human renal hypodysplasia in a minor subset of individuals.

Scores and stages in nephrology.

In this article we review the most relevant acronyms, scores and classifications in the fields of nephrology and urology, including the newest definitions of acute kidney injury and chronic kidney diseases. We will also present a short overview of the histopathological Lupus nephritis classification, the renal cysts Bosniak classification and the vesicoureteral reflux grading.

Characteristics of Reflux Episodes and Symptom Association in Patients With Erosive Esophagitis and Nonerosive Reflux Disease: Study Using Combined Impedance–pH Off Therapy

We sought to compare reflux and symptom association patterns in patients with nonerosive reflux disease (NERD), erosive esophagitis (EE), and in healthy volunteers (HVs).

Laboratory based investigations for diagnosing gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) still remains the most common out- GI-related condition in the out-patient setting. While primary care physicians often use empiric trials with proton pump inhibitors (PPI trial) to diagnose GERD, often specialised tests are required to confirm or exclude gastroesophageal reflux causing esophageal or extraesophageal symptoms. The most commonly used procedures to diagnose GERD include: conventional (catheter based) pH monitoring, wireless esophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which one to choose.

Characteristics of gastro-esophageal reflux episodes in Barrett's esophagus, erosive esophagitis and healthy volunteers

Gastro-esophageal reflux is considered a major culprit in the pathogenesis of Barrett's esophagus (BE). Still, there is controversy on the role of weakly acidic and weakly alkaline reflux in BE. To compare characteristics of reflux episodes patients with BE, erosive esophagitis (EE), and healthy volunteers (HV).

Population-based trend analysis of laparoscopic Nissen and Toupet fundoplications for gastroesophageal reflux disease

The Nissen and Toupet fundoplications are the most commonly used techniques for surgical treatment of gastroesophageal reflux disease. To date, no population-based trend analysis has been reported examining the choice of procedure and short-term outcomes. This study was designed to analyze trends in the use of Nissen versus Toupet fundoplications, and corresponding short-term outcomes during a 10-year period between 1995 and 2004.

Oesophageal motility and bolus transit abnormalities increase in parallel with the severity of gastro-oesophageal reflux disease

Limited data are available regarding the frequency of oesophageal motility and bolus transit abnormalities in subgroups of patients with gastro-oesophageal reflux disease (GERD).

Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease

ADX10059, a metabotropic glutamate receptor 5 (mGluR5) negative allosteric modulator, has been shown to reduce gastro-oesophageal reflux events and oesophageal acid exposure in patients with gastro-oesophageal reflux disease (GERD) and healthy subjects.

Dental erosion and salivary flow rate in cerebral palsy individuals with gastroesophageal reflux

A high prevalence of gastroesophageal reflux (GERD) has been observed in individuals with cerebral palsy (CP). One of the main risks for dental erosion is GERD. This study aimed to evaluate the presence of GERD, variables related to dental erosion and associated with GERD (diet consumption, gastrointestinal symptoms, bruxism), and salivary flow rate, in a group of 46 non-institutionalized CP individuals aged from 3 to 13 years.

Impedance-pH reflux patterns can differentiate non-erosive reflux disease from functional heartburn patients

Symptom association is important to distinguish non-erosive reflux disease [NERD; abnormal oesophageal acid exposure time (AET) and/or positive symptom association] from functional heartburn (FH; normal AET and negative symptom association). Asymptomatic patients during reflux monitoring are challenging as symptom association cannot be assessed.

Reflux monitoring: pH-metry, Bilitec and oesophageal impedance measurements

Gastro-oesophageal reflux disease (GERD) is a highly prevalent condition in Western countries leading to millions of outpatient visits per year. GERD symptoms including heartburn, regurgitation and chest pain are caused by reflux of gastric content in the oesophagus even in the absence of endoscopically visible mucosal lesions. Several procedures are used to identify gastro-oesophageal reflux, the clinically widely used are: conventional (catheter-based) pH monitoring, wireless oesophageal pH monitoring (Bravo), bilirubin monitoring (Bilitec), and combined multichannel intraluminal impedance-pH monitoring (MII-pH). Each technique has strengths and limitations of which clinicians and investigators should be aware when deciding which to choose in a particular patient. Important is the ability to quantify gastro-oesophageal reflux and evaluate the relationship between symptoms and reflux episodes. The present review summarises the technical aspects in performing and interpreting esophageal reflux monitoring procedures.

Symptoms with acid and nonacid reflux may be produced by different mechanisms

Twenty-four-hour multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring detects both acid and nonacid gastroesophageal reflux episodes. The MII-pH catheter contains six impedance segments placed 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES). A pH electrode at 5 cm above the LES identifies the type of reflux, i.e. acid or nonacid. Patients with acid and nonacid reflux exhibit typical and atypical symptoms often within 5 min following a reflux episode. The aim of this study is to compare the timing of symptoms after reflux episodes in patients with acid and nonacid reflux. Methods include a review of 70 MII-pH tracings (42 females, mean age 40, range 18-85 years) either on (50 points) or off (20 points) acid suppression therapy. Typical (heartburn, regurgitation) and atypical (cough) symptoms with acid or nonacid reflux episodes detected by impedance were analyzed. Symptoms were considered positive with acid reflux if there was a pH drop to <4, plus an MII detected a reflux episode and with nonacid reflux if pH remained >4 and MII detected a reflux episode. The timing of the symptom after each reflux episode was recorded. Symptom perception occurred significantly sooner after acid versus nonacid reflux (P < 0.05). Acid reflux episodes are more likely to be perceived in the first 2 min following the reflux episode. Patients with acid reflux are likely to perceive symptoms earlier, and symptoms with acid and nonacid reflux may be produced by different mechanisms.