Complement activation and blockade in massive post-partum haemorrhage, thrombotic microangiopathy and acute kidney injury: a case report.

BACKGROUND: Thrombotic microangiopathy (TMA)-mediated acute kidney injury (AKI) following massive haemorrhage is a rare but severe complication of the post-partum period. It is associated with a poor renal prognosis and a high risk of end-stage kidney disease. Complement activation may occur in this picture. However, whether complement activation, and thus complement blockade, may be critically relevant in this setting is unknown. CASE PRESENTATION: A 50 year-old woman presented with massive delayed post-partum haemorrhage (PPH). Despite bleeding control and normalization of coagulation parameters, she rapidly developed AKI stage 3 associated with dysmorphic microhematuria and proteinuria up to 2 g/day with the need of renal replacement therapy. Blood tests showed signs of TMA associated with markedly increased sC5b-9 and factor Bb plasma levels, respectively markers of terminal and alternative complement pathway over-activation. This clinical picture prompted us to initiate anti-C5 therapy. sC5b-9 normalized within 12 h after the first dose of eculizumab, factor Bb and C3 after seven days, platelet count after nine days and haptoglobin after 3 weeks. The clinical picture improved rapidly with blood pressure control within 48 h. Diuresis resumed after three days, kidney function rapidly improved and haemodialysis could be discontinued after the sixth and last dose. Serum creatinine returned to normal two years after presentation. CONCLUSIONS: We suggest that massive PPH induced major activation of complement pathways, which ultimately lead to TMA-induced AKI. Various causes, such as oocyte-donation, the potential retention of placental material and the use of tranexamic acid may have contributed to complement activation due to PPH. The prompt administration of anti-C5 therapy may have rapidly restored kidney microcirculation patency, thus reversing signs of TMA and AKI. We propose that complement activation may represent a major pathophysiological player of this complication and may provide a novel therapeutic avenue to improve renal prognosis in TMA-induced AKI following massive PPH.

[Intermittent hemodialysis, irreplaceable in specific cases of severe poisoning]. / L'hémodiayse intermittente, irremplaçable dans certains cas d'intoxications sévères.

The medical practitioner is in general well aware of the indications for hemodialysis in severe, acute or chronic renal insufficiency. Apart from the traditional indications for renal replacement therapy, there are some cases such as metfomin and ethylene glycol poisoning, lithium intoxication severe hypercalcemia and tumor lysis syndrome, in which intermittent hemodialysis is the most effective treatment, or sometimes the only effective one. Although these situations remain infrequent, it is crucial to recognize them as quickly as possible.

[Prevention of cardiac arrhythmias in hemodialysis: what are the modulating factors?]. / Prévention des troubles du rythme cardiaque en hémodialyse: quels sont les facteurs modulables?

Sudden death is the first cause of mortality in patients with end stage renal disease undergoing chronic dialysis treatment. The technique of dialysis as well as the chemical composition of the dialysate can impact on the incidence of cardiac arrhythmias. Pilot studies reveal that the use of an acetate-free dialysate with a downstream filter infusion of sodium bicarbonate, coupled with a modulated potassium-profiled dialysate during hemodialysis, or acetate free biofiltration with potassium profiled dialysate, reduces the incidence of arrhythmias, the QT interval and QT dispersion. The limitation of the ultrafiltration volume during the dialysis session, and the increase in calcium concentration in the dialysate are other possible strategies to reduce cardiac arrhythmias.

[Contrast-induced nephropathy]. / Néphropathie au produit de contraste.

Iodine and gadolinium-based contrast induced nephropathy is the third leading cause of hospital-acquired acute kidney injury. It is essentially observed in patients with defined risk factors and is associated with increased morbidity and mortality. The prevention of contrast induced nephropathy consists in volume expansion through intravenous sodium chloride 0.9% or sodium bicarbonate 1.4%. Comparative randomized controlled trials appear to show a benefit in favor of sodium bicarbonate over saline fluids. According to last evidence, N-acetylcysteine does not provide additional benefit over intravenous fluids.

[Sodium bicarbonate to slow the progression of chronic kidney disease]. / Bicarbonate de sodium pour ralentir la progression de la maladie rénale chronique.

Metabolic acidosis is a prevalent complication in moderate and late stages of chronic kidney disease (CKD). It is established that the correction of metabolic acidosis may improve metabolic bone disorders and protein degradation in the skeletal muscle, two characteristic complications of patients with advanced CKD. In the last 18 months, three randomized controlled trials have drawn the attention on a novel indication to correct metabolic acidosis in these patients, i.e., halting CKD progression. These data show that sodium bicarbonate, a cheap and easily manageable treatment, may delay the progression of CKD and the need of a renal replacement therapy such as dialysis or kidney transplantation.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

The leptin/adiponectin ratio: potential implications for peritoneal dialysis.

Leptin and adiponectin are adipokines with respective pro-atherogenic and anti-atherogenic properties, defining the plasma leptin/adiponectin ratio as a novel marker for atherosclerosis. In non-renal patients, both hyperleptinemia and hypoadiponectinemia are associated with cardiovascular complications. In peritoneal dialysis (PD) patients, the leptin/adiponectin ratio is markedly elevated, which is consistent with their increased cardiovascular risk. As glucose metabolism regulates adipokines, we hypothesized that glucose and/or other PD fluid components may affect adipokine production balance. This review summarizes the available data arising from research in this area. In 3T3-L1 adipocytes, glucose-based PD4 1.36% significantly increased leptin secretion vs amino-acid-based (AA) and icodextrin (ICOD)-based PD fluids. In contrast, adiponectin secretion was significantly reduced by PD4 1.36% vs glucose-free dialysates. Glucose concentration in PD fluids was shown to determine leptin secretion. Preliminary data from PD patients showed that a single 6-h dwell with PD4 3.86% glucose acutely increased plasma leptin vs AA (P<0.05). The reduction in glucose load in a standard PD regimen was associated with an improvement in the plasma leptin/adiponectin ratio at 6 months. pH-neutral PD fluids increased leptin secretion in vitro vs acidic PD fluids, without effect on adiponectin. Whether this effect may have an impact on plasma leptin levels in PD patients is unknown. In conclusion, glucose-based PD fluids worsen the adipokine production balance in vitro while glucose-free solutions improve it. In PD patients, hypertonic glucose-based PD fluids may increase plasma leptin levels. Glucose-sparing PD regimens appear to improve the leptin/adiponectin ratio. However, their potential to reduce cardiovascular complications needs to be demonstrated.

[Chronic kidney disease and antidiabetic treatment]. / Insuffisance rénale chronique et médicaments antidiabétiques.

Diabetic nephropathy is the leading cause of chronic renal failure (CRF) in Europe. About fifty percent of diabetic subjects develop microalbuminuria, which progresses towards established diabetic nephropathy in one third of patients. The treatment of type 2 diabetes in a patient with CRF is a challenge for the general practitioner, because of the accumulation of drugs and/or specific metabolites. Sulfonylureas are associated with an increased risk of hypoglycaemia. Biguanides may exceptionally cause life-threatening lactic acidosis. Glitazones have an interesting profile since they decrease microalbuminuria and blood pressure. However, their safety is not well defined in the context of CRF In the case of severe CRF, only insulin and repaglinide can be recommended.

[Chronic renal failure: what diet?]. / Insuffisance rénale chronique: quel régime?

A low protein diet has been traditionally advocated in patients with chronic renal failure (CRF), in order to slow its progression. However, CRF is often associated with malnutrition, aggravating its prognosis, especially in elderly patients. In severe CRF, the spontaneous reduction of appetite coupled with additional restrictions regarding sodium, potassium and phophates may further impact on nutrition status. The potential benefit of a low protein diet is therefore questionable. We only recommend a moderately restricted protein diet (0,8 g/kg/day) in selected patients with no sign of malnutrition. This strategy, if applied, must be supported by a multidisciplinary approach involving a nephrologist and a specialised dietician. Additional dietary restrictions are not justified, except in particular situations.

[Malnutrition on dialysis: the end of a fatality]. / Dénutrition en diatlyse: vers la fin d'une fatalité.

Protein-energy malnutrition in patients treated with haemodialysis (HD) is a complex, multifactorial and prevalent problem, starting well ahead of the dialysis program. It is associated with an increased morbidity and mortality. Uraemic patients are relatively resistant to nutrients because of metabolism abnormalities. Prevention of malnutrition is therefore more efficient than treatment per se. Classical supplementation including oral nutritional supplements, intradialytic parenteral nutrition and enteral nutrition remain efficient, if applied for a sufficient time. A global approach coupling supplementation and strategies designed to optimise metabolism abnormalities should increase treatment efficacy and improve the outcome and quality of life of these patients.

[Obesity: what impact on renal function?]. / Obésité: quel impact sur la fonction rénale ?

The increasing prevalence of obesity is a major public health concern, affecting more than one third of the Swiss population. The renal effects of obesity per se, independent of hypertenison or diabetes, though, are less known. Obesity is positively correlated with proteinuria and the development of glomerulomegaly and focal segmental glomerulosclerosis. The pathophysiology of the obesity-associated kidney disease is complex, including hemodynamic and physical factors and increased synthesis of vasoactive and fibrogenic substances by adipose tissue. The most important therapeutic approach is weight reduction. Angiotension converting enzyme (ACE) inhibition is effective in reducing proteinuria, but longer follow-up is required to determine the long term benfits of ACE inhibition.

A young man with a renal colic.

We report the case of a 35-year-old man with no cardiovascular morbidity, presenting with acute flank pain, microscopic haematuria and normal blood pressure. Initially diagnosed as a ureteral colic, the patient was recovered 6 weeks later with severe hypertensive crisis. Further investigations revealed a massive renal infarction secondary to medial fibromuscular dysplasia (FMD). Several aspects of this presentation are intriguing. Renal infarcts are usually seen in older patients having cardiac problems and/or major atheromatous plaques. In addition, FMD is mainly observed in young females and rarely progresses to renal artery occlusion. Furthermore, in this case, FMD remained silent until the acute renal infarction occurred, despite a significant kidney size reduction at the time of diagnosis. Finally, the observation of a delayed hypertensive response to a major renovascular insult provides incentives to discuss possible pathophysiological mechanisms involved in renovascular hypertension.

Mechanisms of postprandial hyperglycemia in liver transplant recipients: comparison of liver transplant patients with kidney transplant patients and healthy controls.

Impaired glucose tolerance or diabetes mellitus are frequent complications after organ transplantation, and are usually attributed to glucocorticoid and immunosuppressive treatments. Liver transplantation results in total hepatic denervation which may also affect glucoregulation. We therefore evaluated postprandial glucose metabolism in a group of patients with liver cirrhosis before and after orthotopic liver transplantation. Seven patients with liver cirrhosis of various etiologies, 6 patients having received a kidney transplant, and 6 healthy subjects were studied. Their glucose metabolism was evaluated in the basal state and over 4 hours after ingestion of a glucose load with 6.6 (2) H glucose dilution analysis. The patients with liver cirrhosis were studied before, and again 4 weeks (range 2-6) and 38 weeks (range 20-76, n=6) after orthotopic liver transplantation. Basal glucose metabolism was similar in liver and kidney transplant recipients. Impaired glucose tolerance was present in both groups, but postprandial hyperglycemia was exaggerated and lasted longer in liver transplant patients. Postprandial insulinemia was lower in liver transplant recipients, while C-peptide concentrations were comparable to those of kidney transplant recipients, indicating increased insulin clearance. Glucose turnover was not altered in both groups of patients during the initial 3 hours after glucose ingestion, but was higher in liver transplant early after transplantation during the fourth hour. Postprandial hyperglycemia remained unchanged in liver transplant recipients 38 weeks after liver transplantation, despite substantial reduction of immunosuppressive and glucocorticoid doses. We conclude that liver transplant recipients have severe postprandial hyperglycemia which can be attributed to insulinopenia (secondary, at least in part, to increased insulin clearance) and a late increased glucose turnover. These changes may be secondary to hepatic denervation.

Effects of acidosis on leptin secretion from 3T3-L1 adipocytes and on serum leptin in the uraemic rat.

Marked hyperleptinaemia and metabolic acidosis are common findings in patients with chronic renal failure. In animal models, both leptin administration and acidosis reduce food intake. However, leptin causes loss of body fat, while acidosis induces muscle wasting. Whether a low pH and leptin production are related has not been studied. Leptin secretion was measured in cultured 3T3-L1 adipocytes exposed to acid or control pH for up to 96 h. In addition, serum leptin was compared between acidotic and bicarbonate-treated uraemic Wistar rats using the remnant model. Leptin levels in the culture medium were decreased at an acid pH of 7.1 compared with a control pH of 7.5 at 96 h (562+/-78 and 831+/-103 pg.48 h(-1). well(-1) respectively; mean+/-S.E.M.; P=0.037). Similarly, serum leptin in uraemic rats was found to be lower in the acidotic group than in the bicarbonate-treated group, although this observation fell just short of statistical significance (1273+/-171 compared with 2059+/-376 pg/ml; P=0.07). In conclusion, acidosis decreases leptin secretion from cultured adipocytes. Accordingly, acidotic uraemic rats seem to exhibit lower serum leptin levels than their bicarbonate-supplemented counterparts. This study is the first report providing a link between acidosis and leptin levels.

[Focal cerebral necrosis caused by intraventricular chemotherapy with methotrexate]. / Nécrose cérébrale focalisée secondaire à une chimiothérapie intraventriculaire au méthotrexate.

A 60 year old white woman progressively developed radicular pain and weakness in both legs. A meningeal carcinomatosis was diagnosed, and an intrathecal chemotherapy with methotrexate (M.T.X.) was begun. A catheter was placed in the frontal horn of the right lateral ventricle. One month later, the patient progressively developed inattentiveness and confusion. The examination showed an abulic-hypokinetic syndrome, and a left hemiparesis. A C.T. scan showed a hypodensity in the frontal-lobe white matter on the right, with contrast enhancement surrounding the region of the catheter. Results of cytologic, bacterial and fungal studies of cerebrospinal fluid were negative. The catheter was removed. The patient was treated with prednisone and she improved. This complication is very rare, and is noticed in only 0.6% of patients who had intraventricular M.T.X. therapy. The cause of this syndrome is a displacement of the catheter into parenchyma. This syndrome is distinct from the other complications (meningoencephalitis, leukoencephalopathy, myelopathy).

[Reversible ophthalmoplegia, cerebellar syndrome and vigilance disorders following phenytoin poisoning]. / Ophtalmoplégie, syndrome cérébelleux et troubles de la vigilance réversibles après intoxication à la phénytoïne.

A 20-year-old man developed marked ophthalmoplegia and cerebellar symptoms after suicidal intoxication with phenytoin (maximal plasmatic level 73.6 mg/l). Symptoms of toxicity completely resolved with supportive care and with activated charcoal. The clinical picture of acute phenytoin intoxication is reviewed. The most common disorders are ataxia, nystagmus and mental status changes, but ophthalmoplegia is rare.

Reducing students' fear of mental illness by means of seminar-induced belief change.

Demonstrated that through brief demythologizing, college students' (N = 32) attitudes toward mental illness could be changed significantly in a non-medical model or psychosocial direction and that this attitude change apparently induced students to report a significantly reduced fear of contracting mental illness. Pretest-follow-up data comparisons confirmed the validity of these findings.