Copy-number disorders are a common cause of congenital kidney malformations.

We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched controls (p = 4.8 × 10(-11)). This excess was attributable to known and novel (i.e., not present in any database or in the literature) genomic disorders. All together, 55/522 (10.5%) RHD cases harbored 34 distinct known genomic disorders, which were detected in only 0.2% of 13,839 population controls (p = 1.2 × 10(-58)). Another 32 (6.1%) RHD cases harbored large gene-disrupting CNVs that were absent from or extremely rare in the 13,839 population controls, identifying 38 potential novel or rare genomic disorders for this trait. Deletions at the HNF1B locus and the DiGeorge/velocardiofacial locus were most frequent. However, the majority of disorders were detected in a single individual. Genomic disorders were detected in 22.5% of individuals with multiple malformations and 14.5% of individuals with isolated urinary-tract defects; 14 individuals harbored two or more diagnostic or rare CNVs. Strikingly, the majority of the known CNV disorders detected in the RHD cohort have previous associations with developmental delay or neuropsychiatric diseases. Up to 16.6% of individuals with kidney malformations had a molecular diagnosis attributable to a copy-number disorder, suggesting kidney malformations as a sentinel manifestation of pathogenic genomic imbalances. A search for pathogenic CNVs should be considered in this population for the diagnosis of their specific genomic disorders and for the evaluation of the potential for developmental delay.

Acute interstitial nephritis due to Leptospira grippotyphosa in the absence of Weil's disease.

Anicteric leptospirosis is a self-limited flu-like disease, whereas the icteric form is a severe illness characterized by multiple organ involvement or even failure. A case involving a patient with rapidly progressing renal insufficiency requiring intermittent renal replacement therapy due to Leptospira grippotyphosa in the absence of a Weil's disease is reported.

La leptospirose anictérique est une maladie pseudogrippale spontanément résolutive, tandis que sa forme ictérique est une maladie grave caractérisée par une atteinte multiorganique ou même par une insuffisance. Les auteurs présentent le cas d'un patient présentant une insuffisance rénale à évolution rapide exigeant une thérapie de substitution rénale intermittente attribuable à un Leptospira grippothyphosa en l'absence d'une maladie de Weil.

MRCP-secretin test-guided management of idiopathic recurrent pancreatitis: long-term outcomes.

BACKGROUND: In patients with recurrent pancreatitis of unknown etiology and nondilated ducts, accurate morphofunctional evaluation of the pancreaticobiliary ductal system and sphincter of Oddi function is important in the diagnostic workup. However, ERCP and sphincter of Oddi manometry may be nondiagnostic and postprocedure complications may be frequent. OBJECTIVE: Our purpose was to assess the diagnostic accuracy of the magnetic resonance cholangiopancreatography with secretin test (MRCP-S) in patients with recurrent acute pancreatitis of unknown etiology. Accuracy was established on the basis of ERCP findings and a minimum of 24 months' clinical follow-up. DESIGN: Thirty-seven consecutive patients with intact gallbladder and a nondilated pancreaticobiliary ductal system with nonpathologic EUS findings entered a prospective MRCP-S-guided and ERCP-guided diagnostic and therapeutic study protocol. RESULTS: Patients were followed up for a mean of 31.3 months (range 26-38 months). MRCP-S identified some pancreatic outflow impairment, suggesting morphofunctional dysfunction of either the major or minor papilla, in 12 of 37 patients (32.4%). The addition of ERCP to MRCP-S did not substantially improve the diagnostic yield for the etiology of recurrent pancreatitis, and 13.6% of cases had mild postprocedure pancreatitis. The S-test was abnormal in 12 of 20 cases (60%) in whom some dysfunction of the sphincter of Oddi or minor papilla was assumed on the basis of follow-up findings. The outcome was successful after biliary or pancreatic sphincterotomy in all patients with an abnormal S-test result. Sensitivity, specificity, and positive and negative predictive values of the S-test for the diagnosis of pancreatic outflow impairment at the major or minor papilla were, respectively, 57.1%, 100%, 100%, and 64%. When the test showed an abnormal result, we were unable to distinguish between biliary and pancreatic segment dysfunction of the sphincter of Oddi. CONCLUSIONS: In idiopathic recurrent pancreatitis with nondilated ducts, the MRCP-S-guided approach gave diagnostic accuracy comparable to ERCP with regard to morphologic lesions, and it can be used as an alternative, avoiding ERCP-related complications in the diagnostic phase. An abnormal S-test result showed an excellent positive predictive value and somewhat disappointing negative predictive value for sphincter of Oddi or minor papilla dysfunction and for clinical success of therapeutic endoscopic approach.

Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors.

BACKGROUND: Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypical immunoglobulin light chains (LCs). The aim of this study was to investigate its clinical characteristics and prognostic factors. METHODS: Multicenter study of LCDD with renal and patient survival analyses. RESULTS: Sixty-three cases were studied (age: 58 +/- 14.2; males: 63.5%; kappa/lambda deposition: 68/32%; underlying disorders: multiple myeloma [MM] 65%, lymphoproliferative disorders 3%, idiopathic 32%). Ninety-six percent presented with renal insufficiency (acute, 52%; chronic, 44%), and 84% with proteinuria >1 g/d. During the follow-up, 36 patients reached uremia (incidence rate: 23.7/100 patient-years) and 37 died (17.5/100 patient-years). The factors independently associated with a worse renal prognosis were age (relative risk [RR], 1.05; 95% confidence interval [CI], 1.009 to 1.086) and serum creatinine at presentation (RR, 1.24; 95% CI, 1.02 to 1.5). Those independently associated with a worse patient survival were age (RR, 1.06; 95% CI, 1.03 to 1.1), MM (RR, 2.75; 95% CI, 1.22 to 6.2), and extrarenal LC deposition (RR, 2.24; 95% CI, 1.15 to 4.35). While kappa-LC deposition was more frequently associated with nodular sclerosing glomerulopathy, histological parameters were not predictors of renal/patient prognosis. The survival of the uremic patients undergoing dialysis was similar to that of patients not reaching uremia. CONCLUSION: LCDD is characterized by renal insufficiency with proteinuria and has a severe prognosis. Apart from age, the prognostic factors identified were degree of renal insufficiency at presentation affecting the renal prognosis, underlying hematologic disorder and extrarenal LC deposition affecting the patient prognosis. Dialysis is worth performing in uremic LCDD patients.

Anti-GBM nephritis complicating diabetic nephropathy.

There are several reports of glomerulonephritis (GN) in diabetics or patients with diabetic glomerulosclerosis. Cases of rapidly progressive GN where crescentic histologic changes are superimposed on diabetic glomerulosclerosis are very unusual. We report the case of a patient with type I diabetes mellitus, who developed rapidly progressive renal insufficiency. Renal biopsy disclosed anti-glomerular basement membrane nephritis superimposed on classical diabetic glomerulosclerosis.

Small bowel capsule endoscopy in clinical practice: a multicenter 7-year survey.

BACKGROUND AND AIM: Data about small bowel capsule endoscopy (SBCE) come from studies involving small and highly selected populations. The study aim was to describe extent of use, indications, results, complications, and practical issues of SBCE in clinical practice in a Northern Italian Region (Lombardia). MATERIALS AND METHODS: Twenty-three out of 29 invited centers fulfilled a specific questionnaire. RESULTS: Between 2001 and 2008, 2921 procedures were performed and both the number of centers performing SBCE (from 5 to 29) and the number of SBCE (from 7.2 to 69.2 per month) increased steadily. The main indications for SBCE were: obscure gastrointestinal bleeding (OGIB) (43.4%), unexplained anemia (23.9%), suspected Crohn's disease (7.8%) and abdominal pain (5.3%). Overall, SBCE was positive in 50% of cases, negative in 36% and undefined in 14%. The highest diagnostic yields were observed in patients with OGIB (62.5%), polypoid syndromes (74.1%), known (54.8%) or suspected (47.3%) inflammatory bowel disease, while the yields were low in patients examined for chronic diarrhea (27.4%) and abdominal pain (14.9%), 61 patients (2.1%) experienced capsule retention. Thirty-two of them eventually excreted the capsule naturally while endoscopic or surgical retrieval was necessary in 29 (1%) (in two because of obstruction). CONCLUSION: Over a period of 7 years the use of SBCE in Lombardia increased steadily confirming, in clinical practice, a high diagnostic yield and an acceptable safety profile.

Secretin MRCP and endoscopic pancreatic manometry in the evaluation of sphincter of Oddi function: a comparative pilot study in patients with idiopathic recurrent pancreatitis.

BACKGROUND: Sphincter of Oddi dysfunction plays an important etiologic role in idiopathic acute recurrent pancreatitis. Sphincter of Oddi manometry is the most accurate test of sphincter of Oddi function, but it is associated with an increased risk of post-procedure pancreatitis and is non-diagnostic in about a third of cases. Secretin MRCP has a diagnostic efficacy comparable to ERCP, but data on its sensitivity with regard to sphincter of Oddi function are lacking. The aim of this study was to compare secretin MRCP and pancreatic sphincter of Oddi manometry for evaluation of sphincter of Oddi function in patients with idiopathic acute recurrent pancreatitis. METHODS: Eighteen consecutive patients with idiopathic acute recurrent pancreatitis underwent secretin MRCP and pancreatic sphincter of Oddi manometry/ERCP. Data from 15 patients were suitable for analysis. Fifteen subjects with asymptomatic, non-pancreatic hyperamylasemia matched for age and gender underwent secretin MRCP and served as a control group. RESULTS: Sphincter of Oddi manometry documented sphincter dysfunction in 6/15 patients (40%) and secretin MRCP, in 4/15 patients (26.7%). Sphincter of Oddi manometry confirmed the presence of elevated basal sphincter of Oddi pressure in two of the 4 patients with abnormal and other forms of sphincter of Oddi dyskinesia in the other two. None of the control subjects had an abnormal secretin MRCP. Secretin MRCP and sphincter of Oddi manometry were concordant in 13/15 patients (86.7%); positive and negative diagnoses for sphincter of Oddi dysfunction agreed in, respectively, 81.8% and 100% (kappa value 0.706). CONCLUSIONS: Secretin MRCP seems to be a useful noninvasive procedure for investigation of pancreatic sphincter of Oddi function, but evaluation in larger series is needed.

Comparison of two dosing regimens of gabexate in the prophylaxis of post-ERCP pancreatitis.

OBJECTIVES: A continuous 13-h infusion of gabexate starting 30-90 min before endoscopic cholangiopancreatography (ERCP) can reduce postprocedural pancreatitis, the onset of which is generally observed within the first 6 h after ERCP. This study was designed to verify whether a 6.5-h infusion of gabexate was as effective as a 13-h infusion, at the same concentration, for reducing the incidence of post-ERCP pancreatitis (primary endpoint) and pancreatic hyperenzymemia and pain (secondary endpoints). METHODS: A total of 434 patients (201 male and 233 female; mean age 63.9 yr, range 18-96 yr) scheduled for ERCP were prospectively recruited in 25 Italian centers. Patients were randomized double-blind to two treatment groups. All subjects enrolled were first treated with a 500-mg continuous intravenous infusion of gabexate, starting 30 min before the endoscopic maneuvers and continuing up to 6.5 h after it. Over the next 6.5 h, 214 patients (group I) continued the infusion of gabexate (for a total of 1 g over 13 h) and 220 patients (group II) were given placebo (saline solution). RESULTS: The overall incidence of acute pancreatitis was 1.8% (eight patients), which included 1.4% in group I (three of 214 patients) and 2.2% in group II (five of 220 patients). Serum amylase and lipase values over time, peak levels of the two enzymes, pancreatic pain, and need for analgesics did not significantly differ in the two groups. CONCLUSIONS: These results suggest that a 6.5-h infusion of gabexate (for a total of 500 mg) is not less effective than a 13 h infusion, with evident savings.