Search

International audience

BACKGROUND: The course of autosomal dominant polycystic kidney disease (ADPKD) is often associated with pain, hypertension, and kidney failure. Preclinical studies indicated that vasopressin V 2 -receptor antagonists inhibit cyst growth and slow the decline of kidney function. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled, 3-year trial, we randomly assigned 1445 patients, 18 to 50 years of age, who had ADPKD with a total kidney volume of 750 ml or more and an estimated creatinine clearance of 60 ml per minute or more, in a 2:1 ratio to receive tolvaptan, a V 2 -receptor antagonist, at the highest of three twice-daily dose regimens that the patient found tolerable, or placebo. The primary outcome was the annual rate of change in the total kidney volume. Sequential secondary end points included a composite of time to clinical progression (defined as worsening kidney function, kidney pain, hypertension, and albuminuria) and rate of kidney-function decline. RESULTS: Over a 3-year period, the increase in total kidney volume in the tolvaptan group was 2.8% per year (95% confidence interval [CI], 2.5 to 3.1), versus 5.5% per year in the placebo group (95% CI, 5.1 to 6.0; P

Article-at-a-Glance Background There is little evidence for solutions to improve the handoff process between units, particularly from the emergency department (ED) to the inpatient unit. A systematic approach was used to improve the handoff communication process between the ED and the four private physician groups serving Juneau, Alaska, that admit and deliver care to patients of a 73-bed, Level 4 trauma center community hospital. Methods Data were collected in using the Joint Commission Center for Transforming Healthcare's Targeted Solutions Tool® (TST®) to determine the rate of defective handoff communications and the factors that contributed to those defective handoff communications. Targeted solutions were then implemented to specifically address the identified contributing factors. Results A random sample of 107 handoff opportunities was collected during the baseline phase (November 4, 2011–January 12, 2012) to measure performance and identify the contributing factors that led to defective handoffs. The baseline handoff communications defective rate was 29.9% (32 defective handoffs/107 handoff opportunities). The top four contributing factors, together accounting for 69.8% of all the causes of defective handoffs, were inaccurate/incomplete information, method ineffective, no standardized procedures for an effective handoff, and the person initiating the handoff, known as the "sender," lacks knowledge about the patient. After implementation of targeted solutions to the identified contributing factors, the handoff communications defective rate for the "improve" phase (April 1, 2012–July 29, 2012) was reduced from baseline by 58.2% to 12.5% (13 defective handoffs/104 handoff opportunities), p = 0.002; 2-proportions test). The number of adverse events related to handoff communications declined as the handoff communications defective rate improved. Conclusion Use of the TST was associated with improvement in the ED handoff communication process.

In a 70 year old man with primary glomerulonephritis, severe anemia occurred after 4 years on hemodialysis and rHu-EPO. The usual mechanisms of EPO-resistance were excluded. A bone marrow sample showed red all aplasia. No circulating EPO could be detected; the serum inhibited the growth of erythroid precursors in bone marrow cultures. Immunoprecipitation identified an IgG anti-EPO, still active against deglycosylated EPO, i.e. directed against the peptidic matrix. Its high neutralising capacity and the absence of any immune abnormality rule out an auto-antibody. Anti-rHu EPO immunisation is a very rare occurrence, made severe by transfusion-dependence and the risk of hemosiderosis. An immuno-modulating treatment can therefore be justified.

International audience; OBJECTIVE AND METHODS: The aim of this study was to describe the main features of sclerosing peritonitis, using a retrospective study in 10 patients. RESULTS: The main causes of sclerosing peritonitis were continual ambulatory peritoneal dialysis (n = 3), peritoneal chemotherapy (n = 2) and liver cirrhosis (n = 2). Sclerosing peritonitis was revealed by acute or chronic bowel obstruction (n = 8). Small bowel X-rays and abdominal tomodensitometry showed a small bowel dilatation with a normal mucosa (n = 7), ascites (n = 5) as well as agglutination and fixation of small bowel loops within a cocoon (n = 3). Surgical viscerolysis was performed in 9 patients and allowed prolonged clinical remission in 4; 3 patients died postoperatively (1 had a cirrhosis and 2 were treated with continuous ambulatory peritoneal dialysis), 1 patient had a complicated postoperative course with recurrent enterocutaneous fistulae. CONCLUSION: Sclerosing peritonitis may be suspected in a patient who presents a combination of bowel obstruction, small bowel dilatation without mucosal disease and ascites. Surgical viscerolysis is a dangerous operation associated with high mortality in patients with renal failure or cirrhosis.

OBJECTIVE--To compare the ability of angiotensin converting enzyme inhibitors and beta blockers to slow the development of end stage renal failure in non-diabetic patients with chronic renal failure. DESIGN--Open randomised multicentre trial with three year follow up. SETTING--Outpatient departments of six French hospitals. PATIENTS--100 hypertensive patients with chronic renal failure (initial serum creatinine 200-400 mumol/l. 52 randomised to enalapril and 48 to beta blockers (conventional treatment). INTERVENTIONS--Enalapril or beta blocker was combined with frusemide and, if necessary, a calcium blocker or centrally acting drug in patients whose diastolic pressure remained above 90 mm Hg. RESULTS--17 patients receiving conventional treatment and 10 receiving enalapril developed end stage renal failure. The cumulative renal survival rate was significantly better in the enalapril group than in the conventional group (P < 0.05). The slope of the reciprocal serum creatinine concentration was steeper in the conventionally treated patients (-6.89 x 10(-5)l/mumol/month) than in the enalapril group (-4.17 x 10(-5)l/mumol/month; P < 0.05). No difference in blood pressure was found between groups. CONCLUSION--In hypertensive patients with chronic renal failure enalapril slows progression towards end stage renal failure compared with beta blockers. This effect was probably not mediated through controlling blood pressure.

Three patients presented with renal or more diffuse tissue deposits of a nonamyloid material reactive with anti-κ antibody by immunofluorescence. All patients had progressive renal failure with the nephrotic syndrome and extensive tubular basement membrane deposits. Glomerular lesions were conspicuous but heterogeneous. One patient also had hepatic deposits with peliosis at histopathologic examination. An underlying lymphoplasmacytic disorder was found in all patients: multiple myeloma in one, pleomorphic lymphoplasmacytic malignancy analogous to Waldenstrom's macroglobulinemia in one and bone marrow monoclonal plasmacytosis without overt myeloma in one. Biosynthesis experiments in two cases showed production of abnormal κ chains which were not detected in appreciable amounts in serum and urine. These light chains had an aberrant size (abnormally short or large), their apparent molecular weight was larger in secretion than in cytoplasmic extracts (suggesting their glycosylation) and they were secreted as polymers. These results suggest a causal relationship between production of abnormal light chains and tissue deposition.

Renal biopsy and clinical data from 60 patients with crescent formation were correlated. Nephropathy was related to infection (15 cases), malignancy (four) and trichlorethylene exposure (two). Four cases had extrarenal signs. Isolated proteinuria was found 0.5-20 yr before biopsy in 16. Only 17 patients had rapidly progressive glomerulonephritis on clinical criteria. Nineteen patients (35%) are alive with functioning kidneys. Outcome was significantly related to percentage crescentic involvement (p less than 0.02) and oliguria (p less than 0.05) and renal function (p less than 0.01) at presentation. Preceding infection was a favourable sign. Extracapilly glomerulonephritis is not a single entity.

This report describes a patient who presented with unusually severe acute post-streptococcal glomerulonephritis with the development of extensive crescents and later tubular damage and interstitial inflammation. Immunofluorescence studies of an early biopsy specimen showed granular deposits of IgG and β1C in glomeruli and no tubular staining. A later biopsy specimen (28 wk) showed diffuse linear staining of tubular basement membranes, indicating in vivo bound anti-TBM antibodies. At this time the patient's serum IgG was shown by indirect immunofluorescence to react with normal tubular basement membranes. It is proposed that the initial renal disease somehow triggered the formation of anti-TBM antibodies which may have contributed to the progress of the disease.

Renal biopsy and autopsy specimens were studied in 43 patients with renal complications of multiple myeloma and correlated with immunoelectrophoresis (IEP) and other clinical data at the time of biopsy. Lesions specifically related to multiple myeloma fell into two categories, with different patterns of protein excretion. (1) Myeloma Cast Formation: When other lesions which might contribute to renal insufficiency (RI) were excluded, there was a good correlation between the extent of myeloma cast formation and severity of RI. Sixteen of 19 patients excreted free light chains (LCs) in the urine, in seven as the predominant or sole urinary protein. (2) Tissue Deposition of Paraproteins: Nine cases had generalized glomerular, tubular basement membrane and vascular deposits of presumed κ-chains (one with associated alpha-heavy chains). Four patients, all with myelomas secreting lambda LCs, had diffuse amyloid deposits in similar distribution. All patients (save two who were anuric) had diffuse, nonselective proteinuria by IEP, most within the nephrotic range. Four patients had free LCs in the urine, but in none was this the predominant component. Cast nephropathy and LC tissue deposition tended to occur in mutually exclusive fashion. Cases with diffuse tissue deposits of LCs showed few or no myeloma casts. Cases with cast nephropathy had only occasional mild mesangial lesions and focal interstitial and vascular deposits of amyloid. Evidence indicates that these lesions represent incidental LC deposition in cases whose basic lesion is longstanding and/or severe cast nephropathy, and that their contribution to RI is minor in comparison to that of the myeloma casts. However, repeat specimens in six patients reveal that the basic pattern of lesions may change under therapy. All six had typical myeloma cast nephropathy on initial biopsy. Myeloma casts were markedly diminished or absent on repeat examination in all six, but in three cases they were replaced by massive tissue deposits of LCs (κ-chains in two, amyloid in one). The LC electrophoretic mobility (LCEM) was examined in 17 patients with arcs representing free LCs identifiable on serum or urine IEP The LCEM parallels the relative anionic charge/unit mass of the LCs. Cases with high LCEMs, and hence highly anionically charged, usually did not show typical myeloma casts, but might have extensive renal deposits of LCs. Cases with lower LCEMs had typical dense myeloma casts, progressively more prominent as the LCEM decreased. There was an excellent correlation between decreasing LCEM and increasing severity of RI. The explanation for these observations may be related to the charge of the LC at physiologic pH. Those with high LCEMs would be strongly negatively charged and, particularly if polymerized, pass the glomerular filtration barrier less easily than those with lower LCEMs, which would be neutral or even positively charged. This suggestion accords well with the above data indicating that free urinary LCs are an infrequent and minor component of the urinary protein in patients with tissue paraprotein deposits, but are found in the great majority of patients with cast nephropathy, often as the only urinary protein.

Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. As in Hodgkin's disease, the most frequent lesion is minimal-change nephrotic syndrome. Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.

Renal lesions in lymphoid malignancies are rare, with most lesions observed in association with Hodgkin's disease. In two large series of patients with Hodgkin's disease, only 0.4 percent had minimal-change lesion whereas 0.1 percent had amyloidosis. The non-Hodgkin's lymphomas and leukemias comprise large and heterogeneous groups with equally diverse renal lesions. As in Hodgkin's disease, the most frequent lesion is minimal-change nephrotic syndrome. Also recognized are rare reports of renal disease associated with the atypical lymphoid proliferations of angioimmunoblastic lymphadenopathy, giant lymph node hyperplasia syndrome, and acquired immune deficiency syndrome. Broad generalizations regarding the pathogenesis of renal disease in these syndromes are difficult, partly due to the paucity and sporadic reporting of such cases. Mechanisms proposed to explain the renal pathologic findings include autologous nontumor antigens, tumor antigens, fetal antigen expression, immune complex deposition, viral antigens, and disordered T cell function.