[Thrombotic microangiopathy: when time is the key factor!]. / Microangiopathie thrombotique: quand le temps presse.

Thrombotic microangiopathy or "TMA" including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) became a public health problem following the European outbreak of E. coli (O104:H4) gastroenteritis in 2011. A rapid diagnosis and therapy in an intensive care unit provide better patient survival and lower cost for society. Supportive treatment has significantly improved the prognosis over the past decade and includes fresh frozen plasma for TTP, plasmapheresis for HUS, and recently a new therapeutic agent: anti-C5 antibodies. We will provide in this article, through the current literature and four cases encountered in our department, to establish an algorithm to manage patients with TMA.

[Geriatric patients with chronic kidney insufficiency: which antalgia?]. / Patients gériatriques insuffisants rénaux chroniques: quelle antalgie ?

Pain is a leading cause of office visits. In the geriatric population, it is known that the prevalence of renal failure increases exponentially with age, modifing the elimination of drugs and of their metabolites. What analgesia should be offered to these patients? The holy grail would be a medication without renal elimination, without toxic metabolites and without nephrotoxicity. Based on the literature we try to propose a specific approach to analgesia in older patients with kidney insufficiency, in order to help practitioners to better prescribe for this group of patients.

Life-threatening complications of hepatitis B virus-related polyarteritis nodosa developing despite interferon-alpha2b therapy: successful treatment with a combination of interferon, lamivudine, plasma exchanges and steroids.

Polyarteritis nodosa (PAN) is a rare vasculitis associated with hepatitis B virus (HBV) infection in a significant proportion of cases. When used to treat HBV-related PAN, immunosuppressive agents may enhance viral replication and relaspes are frequent. In recent years the use of antiviral drugs has been proposed. We report the case of a patient with HBV-related PAN who, despite 6 weeks of interferon-alpha2b (IFN-alpha2b) monotherapy, developed life-threatening complications with bowel perforation. He was thereafter successfully treated with a combination of IFN-alpha2b, lamivudine, plasma exchanges and short-term steroids. In contrast to IFN-alpha2b, lamivudine is effective in rapidly suppressing viral replication. This may be valuable in the treatment of HBV-related PAN by contributing to a faster diminution of circulating immune complex levels. This case report highlights the importance of aggressive combined therapy in patients with HBV-related PAN.

Is there a place for duplex screening of brachial artery in haemodialysis patients with vascular access?

BACKGROUND: Vascular access (VA) stenosis with subsequent thrombosis remains one of the major causes of morbidity and hospitalization in haemodialysis patients. The present cross-sectional study was planned in order to analyze the usefulness of brachial artery duplex ultrasound for detection and prediction of vascular access stenoses. METHODS: Color duplex ultrasound (Apogée Cx200, sectorial probe 7.5 MHz) was used to obtain the anatomical pattern of the VA and flow velocity waveforms of the brachial artery in 77 non-selected VA (47 Ciminio-Brescia fistulae and 30 PTFE grafts). In each VA, the resistance index (RI), the mean blood flow rate (Q) and the blood flow ratio index (QI) (QI = VA flow rate/contralateral flow rate) were calculated at the level of the brachial artery. The sensitivity and specificity of these brachial Doppler parameters were calculated for the detection of VA stenosis. In normal VA, positive (PPV) and negative predictive (NPV) values were calculated for the development of clinical stenotic complications 3 months post ultrasound examination. RESULTS: Thirteen of the 77 VA (17%) were identified as stenosed by duplex ultrasound and confirmed by fistulography and/or during surgical exploration. The best screening tests for VA stenosis detection were a QI threshold < 4.0 with a sensitivity and specificity of 69 and 69% and an RI > 0.55 with a sensitivity and specificity of 62 and 66%, respectively. In the VA considered as normal by ultrasound, the prediction of subsequent stenosis within three months post-ultrasound examination gave a PPV of only 18% and 19% for RI and QI, respectively. NPV for RI and QI were 90% and 88%. CONCLUSIONS: While Doppler ultrasound is a useful non-invasive test for the detection of prevalent VA stenosis, our results do not confirm that abnormal brachial Doppler flow parameters can predict short term development of VA stenosis.

Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.

Repeated transient anuria following losartan administration in a patient with a solitary kidney.

We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70-80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.

Diffusion kinetics in blood during haemodialysis and in vivo clearance of inorganic phosphate.

Contradictory data are reported in the literature concerning the diffusion kinetics of inorganic phosphates (iPh) between red blood cells and plasma during haemodialysis. Accordingly, we performed mass balance and equilibration studies to analyze the diffusion kinetics of iPh in vivo and in vitro. Mass balance analysis shows that iPh is only cleared from the plasma volume and thus that it practically does not diffuse from red blood cells to plasma during the short time lapse of blood transit through the haemodialyzer. In vitro equilibration studies of blood drawn at the filter outlet show that at room temperature there is a slow, limited, and almost linear net efflux of iPh during the 4 h that follow blood drawing. Our results point out: (1) that the in vivo clearance of iPh should be exclusively determined as plasma clearance, and (2) that for accurate clearance determinations the iPh concentrations should be measured in blood samples centrifuged within at most 1 h after blood drawing. Whole-blood clearance determinations--as well as the in vitro dialyzer data--largely overestimate (>30%) the real in vivo dialyzer performance.

End-stage renal failure after irbesartan prescription in a diabetic patient with previously stable chronic renal insufficiency.

We report the case of a 78-year-old hypertensive diabetic patient without evidence of renal artery stenosis who had moderate chronic renal insufficiency, which had been stable for several years under low-dose captopril therapy, and who rapidly developed acute renal failure when irbesartan was prescribed. Unfortunately the medication was not stopped promptly and the patient never recovered his basal renal function and had to undergo chronic hemodialysis. This observation emphasizes the importance of a careful monitoring of renal function in patients receiving angiotensin II receptor antagonists.

Water-soluble vitamin levels in patients undergoing high-flux hemodialysis and receiving long-term oral postdialysis vitamin supplementation.

The prescription of multivitamin supplements for dialysis patients is routine practice, but the doses prescribed differ greatly from one dialysis center to another. Few data are available concerning long-term vitamin supplementation and its effects on patients either on high-flux hemodialysis or receiving postdialysis supplementation. For several years, we have systematically prescribed to our patients an oral postdialysis multivitamin supplement containing thiamine hydrochloride 100 mg, riboflavin 20 mg, pyridoxine hydrochloride 50 mg, folic acid 6 mg, and ascorbic acid 500 mg. The aim of this study was to perform a cross-sectional long-term evaluation of the vitamin levels in patients who received this vitamin supplement for at least 12 months. We also were interested in investigating the plasma oxalic acid and total homocysteine levels associated with the long-term prescription of these vitamin supplements. Thirty-three patients on high-flux dialysis were studied. Vitamin levels and/or vitamin-dependent enzymatic activities were within the normal range (N) in all patients. The mean results (+/-SD) were plasma ascorbic acid 13.6 +/- 6.4 mg/L (N > 4), plasma folate 14.1 +/- 1.1 microg/L (N > 3), for vitamin B1, alpha-ETK 1.02 +/- 0.02 (N < 1.18) and ETKo 100 +/- 13 U/L (N > 70), for vitamin B2, alpha-EGR 1.00 +/- 0.07 (N < 1.52) and EGRo 1282 +/- 213 U/L (N > 672), and for vitamin B6, alpha-EGOT 1.34 +/- 0.10 (N < 1.8) and EGOTo 380 +/- 84 U/L (N > 228). Plasma oxalic acid was higher than normal in all patients (mean = 61 +/- 15 micromol/L, N < 33). However, all patients had oxalic acid levels within the range reported in the literature for patients not taking extra ascorbic acid. Mean total homocysteine was 24 +/- 8 micromol/L with only 4 patients (12%) having normal levels (N < 15). In conclusion, the postdialysis supplement given provides adequate vitamin levels in almost all patients in the long term. Postdialysis prescription allows an optimal compliance with the treatment, is well accepted by the patients, and is cost-effective.

[Multi-systemic toxicity of colchicine and renal failure: apropos of a case]. / Toxicité multisystémique de la colchicine et insuffisance rénale: à propos d'un cas.

The use of colchicine can produce various side effects, but multiorgan toxicity is rare. We report the first Swiss case of multiorgan toxicity involving typical neuromuscular lesions. Muscular biopsy is a valuable tool in confirming the diagnosis. Renal insufficiency and hepatobiliary diseases are predisposing factors for such complications. Colchicine pharmacology in the case of renal insufficiency is discussed.

Renal vascular lesions in lupus nephritis.

We retrospectively studied the prevalence, histologic features, clinical correlations, and long-term outcome of the intrarenal vascular lesions of lupus nephritis (LN) in a series of 169 renal biopsies performed between 1980 and 1994 in 132 patients with systemic lupus erythematosus. The most common vascular lesions were nonspecific sclerotic changes, found in 37% of the biopsies (24% if only the cases with moderate to severe changes are considered). The other common vascular lesions were "immunoglobulin microvascular casts," found in 24% of the biopsies. Vasculitis and thrombotic microangiopathy were rare lesions and were seen in only 4 (2.4%) and 1 (0.6%) cases, respectively. Isolated sclerotic vascular changes were present in biopsies from older patients with a longer duration of LN, compared with the group with no vascular lesions, and were associated with a significantly higher prevalence of hypertension. Overall, however, the long-term renal and patient survival of this group did not differ significantly from that of the patients without vascular changes. Immunoglobulin microvascular casts (IMCs) ("lupus vasculopathy") were characterized by the presence of immunoglobulin deposition within the glomerular capillaries and small arterioles. In the present study we extensively investigated the morphologic and immunologic features of this lesion. The lesions were notable for the absence of endothelial or parietal vascular lesions and of fibrin, platelets, and leukocytes, which indicates that thrombosis is not involved in the vascular obstruction. According to our data immunoglobulin precipitation in the microvasculature seems to play a central role in the pathogenesis of this lesion, which is why we propose the term "immunoglobulin microvascular casts." In general, IMCs were associated with the most severe and active forms of diffuse proliferative lupus nephritis (World Health Organization [WHO] class IV). However our data show that, in contrast to previous studies, the long-term outcome of patients with IMCs is not worse than that of other patients with class IV LN. It may even be somewhat better, suggesting that this type of lesion may reverse with immunosuppressive therapy. In addition, we did not find any association between the presence of IMCs and the lupus anticoagulant, IgG anticardiolipin antibodies, or extrarenal vascular manifestations. Concerning vasculitis and thrombotic microangiopathy, our results confirm that their occurrence is quite rare in-lupus nephritis. The outcome of our 4 patients with vasculitis was not particularly poor, which could be related to early and/or aggressive treatment. Taken as a whole, our data confirm that the presence of active and severe forms of diffuse proliferative LN (WHO class IV) carries a worse prognosis compared with the other forms of LN. In our study, and in agreement with previous reports (23), the long-term renal survival of patients with class IV LN was significantly worse than that of patients with other forms of LN, with a 10-year renal survival of 70% compared with 85%, respectively. However our data do not support the conclusions of some previous studies that the presence of intrarenal vascular lesions is a marker of poor renal prognosis in lupus nephritis. More precisely, our data show that the somewhat poorer renal outcome observed in patients with IMCs is related to the fact that in most cases these lesions are associated with class IV lupus nephritis, and not related to the presence of the vascular lesion per se.

Transbronchial lung biopsy: an analysis of 530 cases with reference to the number of samples.

To evaluate the diagnostic yield (DY) of transbronchial lung biopsies (TBBs), as the relationship between the DY and the number of tissue specimens taken per TBB, we reviewed the histological and clinical data of 530 consecutive TBBs performed in 516 immunocompetent patients, having either a chronic diffuse lung infiltrate, a localized peripheral lung lesion or hilar adenopathies. The DY (positive TBBs/performed TBBs) varied significantly according to the radiographic pattern and the underlying disease. For chronic diffuse pulmonary infiltrates (n = 244), the overall DY was 50%, but higher figures were obtained for hypersensitivity pneumonitis (92%), sarcoidosis stage II-III (75%), lymphangitic carcinomatosis (68%) and pneumoconiosis (54%). The DY was lower in diffuse tuberculosis (38%) and interstitial pulmonary fibrosis (27%). For localized peripheral lung lesions (n = 205), the overall DY was only 29%, while for sarcoidosis stage I it was 56% (n = 63). Data analysis shows that there is a direct correlation between the number of samples obtained per TBB and the overall DY (i.e. 38% with one to three tissue fragments versus 69% with six to 10, p < 0.01). The increment itself depends on the radiographic pattern and/or the underlying disease which indicates that the probability of diagnostic confirmation per individual tissue sample is not always the same. The clinical implication of these findings is that whereas for some pulmonary diseases the DY is already good with few samples, more samples are to be taken to warrant a satisfactory overall DY. Accordingly, we recommend that at least five to six specimens per TBB should be taken. This number should allow a quite good overall DY in patients with diffuse lung infiltrate. On theoretical grounds, more specimens (seven to 10) should be taken for an optimal DY of localized peripheral lung lesions and of sarcoidosis at stage I. In these indications the clinician should therefore compare the risk-benefit of TBB with a high number of biopsies to the results of other diagnostic procedures.

High frequency of marked hyperphosphatemia during intravenous calcitriol therapy in hemodialysis patients with refractory hyperparathyroidism.

Efficacy and safety of intermittent intravenous calcitriol therapy were studied in 8 chronic hemodialysis patients with marked hyperparathyroidism refractory to oral therapy with calcium salts and daily vitamin D. They were followed for 20 weeks (32 weeks for 2 patients). At the start of the study, serum calcium was < 2.65 mmol/l and phosphate levels were controlled with calcium-based binders only. The phosphate content of the prescribed diet (< 1 g/day) remained unchanged during the study, and a low-calcium dialysate was used (1.38 mmol/l). The initial postdialysis calcitriol dose was 1 microgram and was increased to 2 micrograms in 6 patients. Intravenous calcitriol effectively improved hyperparathyroidism in 7 patients, with a significant decrease of the intact parathyroid hormone level from 650 +/- 433 to 195 +/- 208 pg/ml (p < 0.05). Hypercalcemia > 2.7 mmol/l occurring in 3 patients was observed in only 11% of the weekly laboratory controls and always resolved rapidly. In contrast, hyperphosphatemia > or = 2.0 mmol/l was observed in 7 patients and in 40% of the weekly laboratory controls. In 15% of the cases the phosphate values even exceeded 2.4 mmol/l. The phosphate binder therapy had to be intensified accordingly, not only by increasing the dose of calcium-based binders, but also by introducing aluminum salts in 6 patients. In summary, our data show that intravenously administered calcitriol is effective in the treatment of severe hyperparathyroidism in most hemodialysis patients resistant to oral therapy. However, its usefulness seems to be limited by frequency and severity of hyperphosphatemia, frequently necessitating additional prescription of aluminum-based binders. These undesirable secondary events may thus limit the long-term utility of intravenously administered calcitriol.