Contribution of Raman spectroscopy in nephrology: a candidate technique to detect hydroxyethyl starch of third generation in osmotic renal lesions.

BACKGROUND AND OBJECTIVES: HydroxyEthyl Starch (HES) has been one of the most commonly used colloid volume expanders in intensive care units for over 50 years. The first and second generation HES, with a high molecular weight (≥200 kD) and a high degree of substitution (≥0.5), has been associated with both renal dysfunction and osmotic nephrosis-like lesions in histological studies. Recently, third generation HES (130 kD/<0.5) has also been shown to impair renal function in critically ill adult patients although tubular accumulation of HES has never been proven in the human kidney. Our objective was to demonstrate the potential of Raman micro-imaging to bring out the presence of third generation-HES in the kidney of patients having received the volume expander. DESIGN: Four biopsies presenting osmotic nephrosis-like lesions originated from HES-administrated patients with impaired renal function were compared with HES-negative biopsies (n = 10) by Raman microspectroscopy. RESULTS: The first step was dedicated to the identification of a specific vibration of HES permitting the detection of the cellular and tissue accumulation of the product. This specific vibration at 480 cm(-1) is assigned to a collective mode of the macromolecule; it is located in a spectral region with a limited contribution from biological materials. Based on this finding, HES distribution within tissue sections was investigated using Raman micro-imaging. Determination of HES positive pixels permitted us to clearly distinguish positive cases from HES-free biopsies (proportions of positive pixels from the total number of pixels: 23.48% ± 28 vs. 0.87% ± 1.2; p = 0.004). CONCLUSIONS: This study shows that Raman spectroscopy is a candidate technique to detect HES in kidney tissue samples currently manipulated in nephrology departments. In addition, on the clinical aspect, our approach suggests that renal impairment related to third generation HES administration is associated with osmotic nephrosis-like lesions and HES accumulation in the kidney.

Nephropathia epidemica and leptospirosis in Champagne-Ardenne, France: comparison of clinical, biological and epidemiological profiles.

In the present retrospective study, we described a series of 45 non-icteric leptospirosis and 44 nephropathia epidemica (NE) patients diagnosed in the northeast of France from 1995 to 2005 and compared their clinical picture and laboratory parameters, as well as some epidemiological data. Loin pain (P < 0.001), abdominal pains (P = 0.007), rise of blood pressure (P < 0.001) and pharyngitis (P = 0.01) were more frequently found in NE patients. Aspartate aminotransferase (ASAT) (P = 0,006), creatine phosphokinase (CPK) (P < 0.0001) and C-reactive protein (CRP) (P < 0.0001) were higher in leptospirosis, whereas creatinine (P = 0.009) was higher in NE. Leptospirosis mainly concerns occupational hazards, e.g. farmers, and leisure activities like swimming, and NE concerns professional foresters or leisure activities in the forest and the cleaning of attics. During hospitalisation, patients receiving antibiotics were more frequent among leptospirosis than among NE patients (80% versus 59%, P = 0.06). Among the various common clinical signs, only acute myopia appeared to be a pathognomonic but inconsistently observed clinical sign, which was only observed in 47% of NE cases.

Investigation of nosocomial pneumocystis infections: usefulness of longitudinal screening of epidemic and post-epidemic pneumocystis genotypes.

BACKGROUND: Twenty-five patients, of whom 22 were renal transplant recipients, developed Pneumocystis jirovecii infections at the nephrology department of Reims University Hospital (France) from September 2008 to October 2009, whereas only four sporadic cases had been diagnosed in this department over the 14 previous years. AIM: This outbreak was investigated by analysing patient encounters and P. jirovecii types. METHODS: A transmission map was drawn up. P. jirovecii typing at DHPS, ITS and mtLSU rRNA sequences was performed in the patients of the cluster (18 patients with Pneumocystis pneumonia (PCP) and seven colonized patients), 10 unlinked control patients (six PCP patients and four colonized patients), as well as 23 other patients diagnosed with P. jirovecii (nine PCP patients and 14 colonized patients) in the same department over a three-year post-epidemic period. FINDINGS: Eleven encounters between patients harbouring the same types were observed. Three PCP patients and one colonized patient were considered as possible index cases. The most frequent types in the cluster group and the control group were identical. However, their frequency was significantly higher in the first than in the second group (P < 0.01). Identical types were also identified in the post-epidemic group, suggesting a second outbreak due to the same strain, contemporary to a disruption in prevention measures. CONCLUSIONS: These results provide additional data on the role of both PCP and colonized patients as infectious sources. Longitudinal screening of P. jirovecii types in infected patients, including colonized patients, is required in the investigation of the fungus's circulation within hospitals.

[Paraneoplastic nephrotic syndrome associated with broncho-pulmonary cancer]. / Syndrome néphrotique paranéeoplasique et cancers broncho-pulmonaires. 3 observations et revue de la littérature.

INTRODUCTION: Paraneoplastic nephrotic syndrome associated with malignant broncho-pulmonary tumors. Three cases and literature review. Malignant broncho-pulmonary tumours are the principal cause of a paraneoplastic nephrotic syndrome. These tumours are most often small cell or squamous bronchial carcinomas. In 75% of cases the nephrotic syndrome is due to a membranous glomerulonephritis and it usually precedes the discovery of the causative tumour. CASES REPORT: Three cases of paraneoploastic nephrotic syndrome associated with bronchial carcinoma are described. The first is of a bronchial carcinoid tumour associated with a membrano-proliferative glomerulonephritis. In the second a bronchial adenocarcinoma was revealed by a membranous glomerulonephritis. The last case concerns a squamous carcinoma associated with a nephrotic syndrome in which the histological lesions were not documented on account of progression to rapidly fatal acute renal failure. CONCLUSION: A revue of the literature describes the associations between paraneoplastic nephrotic syndrome and bronchial carcinoma.

Cardiac troponin-I on diagnosis predicts early death and refractoriness in acquired thrombotic thrombocytopenic purpura. Experience of the French Thrombotic Microangiopathies Reference Center.

BACKGROUND: Cardiac involvement is a major cause of mortality in patients with thrombotic thrombocytopenic purpura (TTP). However, diagnosis remains underestimated and delayed, owing to subclinical injuries. Cardiac troponin-I measurement (cTnI) on admission could improve the early diagnosis of cardiac involvement and have prognostic value. OBJECTIVES: To assess the predictive value of cTnI in patients with TTP for death or refractoriness. PATIENTS/METHODS: The study involved a prospective cohort of adult TTP patients with acquired severe ADAMTS-13 deficiency (< 10%) and included in the registry of the French Reference Center for Thrombotic Microangiopathies. Centralized cTnI measurements were performed on frozen serum on admission. RESULTS: Between January 2003 and December 2011, 133 patients with TTP (mean age, 48 ± 17 years) had available cTnI measurements on admission. Thirty-two patients (24%) had clinical and/or electrocardiogram features. Nineteen (14.3%) had cardiac symptoms, mainly congestive heart failure and myocardial infarction. Electrocardiogram changes, mainly repolarization disorders, were present in 13 cases. An increased cTnI level (> 0.1 µg L(-1) ) was present in 78 patients (59%), of whom 46 (59%) had no clinical cardiac involvement. The main outcomes were death (25%) and refractoriness (17%). Age (P = 0.02) and cTnI level (P = 0.002) showed the greatest impact on survival. A cTnI level of > 0.25 µg L(-1) was the only independent factor in predicting death (odds ratio [OR] 2.87; 95% confidence interval [CI] 1.13-7.22; P = 0.024) and/or refractoriness (OR 3.03; 95% CI 1.27-7.3; P = 0.01). CONCLUSIONS: A CTnI level of > 0.25 µg L(-1) at presentation in patients with TTP appears to be an independent factor associated with a three-fold increase in the risk of death or refractoriness. Therefore, cTnI level should be considered as a prognostic indicator in patients diagnosed with TTP.

Long-term follow-up of acute renal failure caused by angiotensin converting enzyme inhibitors.

Angiotensin converting enzyme (ACE) inhibitors are useful in the treatment of hypertension and heart failure. However, acute renal failure (ARF) may occur in patients who are taking these drugs in situations associated with decreased glomerular filtration pressure, such as dehydration caused by acute diarrhea or diuretic therapy. Sixty-four patients who were admitted to the intensive care unit for ARF associated with ACE inhibitor therapy were followed for more than 5 years. In this historical retrospective study, we documented that 45 patients were treated for hypertension (group I) and 19 were treated for heart failure (group II). Their mean age was 71.2+/-11.6 years. Patients with ARF presented with overt dehydration in 91% and 84% of the cases in groups I and II, respectively. Hypovolemia was caused by diuretics or gastrointestinal fluid loss. Bilateral artery-renal stenosis or stenosis in a solitary kidney was documented in 22% and 10% of patients in groups I and II, respectively. The probability of survival was 91% and 49% at 1 year and 64% and 18% at 5 years, for groups I and II, respectively. Acute renal failure required hemodialysis in seven patients, but none of them became dialysis dependent. In the subgroup of patients with preexisting chronic renal failure, all the patients except for one who belonged to group II died within 2 years. In both groups, after resolution of ARF, plasma creatinine concentration returned to baseline level and the course of renal function was not significantly worsened. In conclusion, ARF associated with ACE inhibitors is likely to occur in many patients without renal artery stenosis after unexpected dehydration, especially in older patients with congestive heart failure. In both groups of patients, in the absence of preexisting chronic uremia, recovery of renal function occurred without sequelae, even after an episode of acute tubular necrosis requiring dialysis.

Assessment of acetate free continuous veno-venous hemofiltration in acute renal failure.

Among the limitations of continuous renal replacement therapy (CRRT) in patients with severe acute renal failure (ARF) and cardiovascular instability is the use of acetate in the substitution fluid. Acetate is required to maintain acidity of the polyelectrolytic solution to avoid calcium carbonate precipitation in the presence of bicarbonate. In addition, in patients with cardiovascular instability, acetate metabolism is impaired and further compromises hemodynamics. A new CRRT technique is proposed in which bicarbonate is used as a buffer, but the acetate requirements are cancelled: acetate free veno-venous hemofiltration (AF-CVVH). This technique allows control of acid-base disturbances independent of urea removal. This preliminary report describes the feasibility of the technique based on separate infusion of water and electrolytes administered prefiltration, and isotonic sodium bicarbonate administered post filtration. The setting of the technique, adapted to the PRISMA device (Hospal, Lyon, France), was based on a model predicting the bicarbonate infusion rate for a target plasma bicarbonate level. The AF-CVVH was compared with conventional, continuous veno-venous hemofiltration (CVVH) in a crossover study that showed AF-CVVH allowed fastest control of acidosis, avoiding 70 to 80 mmol/d of acetate transfer to the patient. Urea removal was similar with both techniques. It was concluded that AF-CVVH, when compared with CVVH, has the main advantage of separately controlling urea retention and metabolic acidosis in patients with severe ARF and cardiovascular instability.

[Treatment of legionellosis with ofloxacin in kidney transplanted patients. Lack of interaction with cyclosporin A]. / Traitement des légionelloses par ofloxacine chez le transplanté rénal. Absence d'interférence avec la ciclosporine A.

Seven cases of legionellosis were observed in a series of 81 renal transplant recipients. In the 6 patients with functional graft, pneumonia occurred 17 days on average after the beginning of transplant rejection treatment. The diagnosis was made by bronchoalveolar lavage: the direct immunofluorescence antigen technique was positive in 5 cases and culture in 6 cases. Legionella pneumophila sero-groups 5 and 1 were identified in one and 5 patients respectively. Six of the 7 patients were treated with ofloxacin. This fluoroquinolone was effective in all cases. It was administered as single therapy in 3 patients and did not interfere with ciclosporin A metabolism. Ofloxacin given in mean doses of 400 mg per day adjusted to renal function proved to be a simple, effective and well tolerated treatment of legionellosis in transplant recipients receiving ciclosporin A.

[Cytomegalovirus infection, a risk factor for acute graft rejection in renal transplant recipients. A case-controlled study]. / La maladie à cytomégalovirus, facteur de risque de rejet aigu d'allogreffe rénale. Etude exposés/non exposés.

OBJECTIVES: We studied the relationship between cytomegalovirus infection and episodes of acute rejection after infection in renal graft recipients at the Reims University Hospital from 1989 to 1995. PATIENTS AND METHODS: Two exposed versus nonexposed analyses were conducted, one (series 1) for CMV infection and the other (series 2) for CMV disease. For each analysis, exposed recipients were matched with nonexposed recipients for date of graft (+/- 6 months). Risk of acute rejection was assessed with univariate analysis then with multivariate analysis using logistic regression. RESULTS: Among the 192 graft recipients included, 64 developed CMV infection, 77 had an infection (series 1) and 51 had CMV disease (series 2). In series 1, only failure of renal graft was a significant risk factor of acute rejection (OR = 10.4; 95% Cl 1.9-56.3). CMV infection was not a significant risk factor (OR = 1.06; 95% Cl 0.2-5.6). Conversely, in series 2, there was a 6-fold increase in the risk of acute rejection in recipients who developed CMV disease (OR = 5.98; 95% Cl 1.21-29.4). CONCLUSION: The fact that CMV disease and not CMV infection is a risk factor of acute rejection in renal transplant recipients is an argument for implicating a general inflammatory reaction characteristic of CMV disease in the pathogenesis of acute rejection. This finding favors preventive treatment of CMV infection.

[Schoenlein-Henoch purpura as a presentation of squamous cell bronchial carcinoma]. / Purpura rhumatoïde révélateur d'un carcinome épidermoïde bronchique.

Schoenlein-Henoch purpura is a systemic vasculitis involving the small vessels. In adults it is rare and is sometimes associated with malignancies such as bronchial carcinoma. We report the case of a 74-year-old male ex smoker who was admitted with necrotic skin lesions associated with a nephrotic syndrome, and was found to have a right upper lobe squamous cell bronchial carcinoma. The renal biopsy led to a diagnosis of IgA nephropathy related to Schoenlein-Henoch purpura. Curative surgical resection of the bronchial carcinoma (ypT2N0M0) was associated with remission of the purpura. The synchronous diagnosis of bronchial carcinoma and Schoenlein-Henoch purpura suggests a potential relationship between these two pathologies. Our observation and other published data strongly suggest a direct link on account of: the synchronous diagnosis, the clinical and biological remission of the Schoenlein-Henoch purpura after curative treatment of the bronchial carcinoma. It is important to recognise both the therapeutic and prognostic significance of this connection.

Intestinal calcium absorption from mineral water.

Little is known about the bioavailability of calcium in water and various beverages. Some mineral waters contain large amounts of calcium that could compensate for insufficient consumption of dairy products. The fractional intestinal absorption of calcium (FCA) was measured in 12 healthy adult volunteers, using a trace dose of radiocalcium and 200 mg of calcium carrier, part of which was calcium contained in mineral water. Measurements were performed in fasting subjects consuming a standard breakfast. In all the subjects, three mineral waters with a calcium concentration of 10.4, 78, and 467 mg/l, respectively, were tested. Calcium absorption occurred with the same kinetics for each of the mineral waters tested, and within 2 h of the oral dose, equilibrium was reached between absorbed calcium and calcium remaining in the gastrointestinal tract, which resulted in a constant FCA value. This level comprising between 34.1 and 37.0% was independent of the daily calcium consumption and the chemical content of the mineral water. In conclusion, calcium contained in mineral waters in available for intestinal absorption. In a given normal subject, the only rate-limiting factor for FCA is the amount of total calcium given with foods and drinks. Mineral waters containing calcium are recommended as a supplemental source of calcium to achieve optimal calcium requirements, especially in aged people with lactose intolerance.

[Evaluation of the frequency of acute renal insufficiency and therapeutic modalities in the nephrological milieu]. / Evaluation de la fréquence de l'insuffisance rénale aiguë et de ses modalités thérapeutiques en milieu néphrologique.

Due to lack of structured epidemiological studies, the incidence of acute renal failure (ARF) cannot be established in France. An empirical approach method based on answered questionnaire sent by mail to nephrology centers affiliated or not to universities has been used to estimate the frequency of ARF requiring dialysis in 1991. We postulated that the French population was homogeneously distributed among the different regions and that the response rate of 74% could be extrapolated to 100%. We could therefore calculate an incidence of 64 ARF per million of inhabitants. However, this underestimates the exact incidence since the accurate evaluation of IRA in a controlled region (Champagne-Ardenne) is 104 per million of inhabitants. In addition, this study underlines the fact that many ARF are not treated in nephrology units, especially those associated with multiorgan failure requiring slow continuous hemofiltration and hemodialysis. It is suggested that the establishment of a national Registry for ARF and an adequate training of nephrologists are prerequisites to assess epidemiology and the global cost of ARF.

[Continuous hemodialysis with low blood flow and low dialysate flow in the treatment of acute renal insufficiency]. / L'hémodialyse continue à bas débit sanguin et à bas débit de dialysat dans le traitement de l'insuffisance rénale aiguë.

Slow continuous hemodialysis (SCHD) was performed in 9 patients with oliguric acute renal failure and cardiovascular instability. The vascular access was a Scribner's shunt in 7 patients and a double lumen venous catheter with a BSM22 blood system in 2 patients. Three different dialyzers were tested. The mean urea clearance was 10.8 +/- 1.5 ml/min with the 0.2 m2 polysulfone hollow fiber dialyzer, 14.3 +/- 2.7 ml/min with the 0.5 m2 AN 69 S parallel plate dialyzer and 13.8 +/- 1.8 ml/min with the 0.6 m2 AN 69 hollow fiber dialyzer. The mean dialysate flow rate was 15.6 +/- 1.9 ml/min, 15.2 +/- 0.7 ml/min and 15.1 +/- 1.6 ml/min for the three dialyzers, respectively. A linear relationship was documented for blood urea clearance and dialysate flow rate indicating clearly that low blood flow from 60 to 100 ml per min was appropriate for optimal diffusive transfer. The technic required continuous heparin anticoagulation. Three patients died of causes not related to the SCHD technic. When used in critically ill patients, SCHD is a simple method, suitable for intensive care unit staff with no trained dialysis nurses and allows an adequate control of uremia, fluid removal, acid base homeostasis and parenteral nutrition.

[A case of acute myopia with angle-closure glaucoma]. / A propos d'un cas de myopie aiguë avec glaucome par fermeture de l'angle.

The authors report a case of transient myopia with closed angle following the administration of Aspirin and Deturgylone. This treatment was prescribed because of a probably Hantaan virus infection.

Intestinal absorption of calcium from yogurt in lactase-deficient subjects.

Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency.

Kinetics of carbamylated haemoglobin in acute renal failure.

BACKGROUND: Carbamylation of proteins by isocyanic acid, the reactive form of cyanate derived from urea, is increased in uraemia and may contribute to uraemic toxicity. Kinetics of carbamylation that may reflect uraemic toxicity is not clearly defined in acute renal failure (ARF). METHODS: Twenty-eight patients with ARF and 13 with chronic renal failure (CRF) were included in the study in order to determine changes in carbamylated haemoglobin concentration (CarHb) in ARF. The usefulness of this parameter for differentiating ARF from CRF was also investigated. CarHb was measured by high-performance liquid chromatography after acid hydrolysis. RESULTS: Mean CarHb level (expressed as microg carbamyl valine per gram (CV/g) Hb) was significantly higher in ARF (54.3+/-5.2) than in normal subjects (31.6+/-1.3). On admission, CarHb level was correlated with duration of ARF prior to hospitalization in the intensive care unit (r(2)=0.723, P<0.001). CarHb was significantly higher at recovery in the subgroup of patients requiring haemodialysis than in the subgroup not requiring haemodialysis (82. 4+/-11.3 vs 46.7+/-5.2, P<0.01). Similarly dialysis patients lost more weight (8.6+/-1.4 vs 2.7+/-0.5 kg, P<0.005) and had higher averaged blood urea levels in the 20 days prior to recovery (17. 6+/-1.9 vs 11.3+/-1.8 mol/l, P<0.05). After recovery, CarHb level decreased at a rate of 0.219 microg CV/g Hb per day in patients with reversible renal insufficiency. CarHb concentration was higher in patients with CRF. A cut-off CarHb value of 100 microg CV/g Hb had a sensitivity of 94% and a positive predictive value of 94% for differentiating ARF from CRF. CONCLUSIONS: Kinetics of CarHb showed a near normal red blood cell life span in ARF. Changes in CarHb enabled, with a good sensitivity, the distinction to be made between patients who recovered from ARF and those with sustained renal impairment, whether due to prior CRF or resulting from parenchymal sequelae. Measurement of CarHb is valuable at clinical presentation of ARF in patients with an unknown medical history of renal disease.