François Beloncle

Splenectomy and/or cyclophosphamide as salvage therapies in thrombotic thrombocytopenic purpura: the French TMA Reference Center experience

BACKGROUND: The objective was to assess the efficacy and safety of splenectomy and cyclophosphamide as salvage therapies in severe thrombotic thrombocytopenic purpura (TTP).

Does vasopressor therapy have an indication in hemorrhagic shock

This review aimed to answer whether the vasopressors are useful at the early phase of hemorrhagic shock. Data were taken from published experimental studies and clinical trials. Published case reports were discarded. A search of electronic database PubMed was conducted using keywords of hemorrhagic shock, vasopressors, vasoconstrictors, norepinephrine, epinephrine, vasopressin. The redundant papers were not included. We identified 15 experimental studies that compared hemorrhagic shock resuscitated with or without vasopressors, three retrospective clinical studies, and one controlled trial. The experimental and clinical studies are discussed in the clinical context, and their strengths as well as limitations are highlighted. There is a strong rationale for a vasopressor support in severe hemorrhagic shock. However, this should be tempered by the risk of excessive vasoconstriction during such hypovolemic state. The experimental models must be analyzed within their own limits and cannot be directly translated into clinical practice. In addition, because of many biases, the results of clinical trials are debatable. Therefore, based on current information, further clinical trials comparing early vasopressor support plus fluid resuscitation versus fluid resuscitation alone are warranted.

An unexpected cause of progressive renal failure in a 66-year-old male after liver transplantation: secondary hyperoxaluria

BackgroundHyperoxaluria is a rare metabolic disorder characterized by calcium oxalate deposition in different tissues. It is caused either by an inherited disease of oxalate metabolism [primary hyperoxalurias (PH)] or by an acquired disturbance (secondary hyperoxaluria).CaseWe report here an atypical presentation of enteric hyperoxaluria-induced renal failure that occurred after liver transplantation. Despite adapted treatment and intensive haemodialysis, the patient did not recover. This case allows the reviewing of the multiple pathophysiological mechanisms involved in this disease.ConclusionOxalate nephropathy should be considered in the differential diagnosis of acute renal failure, especially when previous renal impairment and fat malabsorption are present. We suggest performing renal biopsy early to allow a prompt diagnosis and therapeutic intervention.

Target blood pressure in sepsis: between a rock and a hard place

The optimal target blood pressure in septic shock is still unknown. Therefore, in a long-term, resuscitated porcine model of fecal peritonitis-induced septic shock, Corrêa and colleagues tested whether different titrations of mean arterial pressure (50 to 60 and 75 to 85 mm Hg) would produce different effects on sepsis-related organ dysfunction. The higher blood pressure window was associated with increased needs for fluid resuscitation and norepinephrine support. However, titrating the lower blood pressure range coincided with an increased incidence of acute kidney injury. In contrast, neither the inflammatory response nor tissue mitochondrial activity showed any difference. This research paper in a clinically relevant model elegantly demonstrates that any standard resuscitation strategy may be a double-edged sword with respect to various therapeutic endpoints. Furthermore, it adds an important piece to the puzzle of the complex pathophysiology of sepsis-related acute kidney injury.

Different Impact of the Number of Organ Failures and Graft-Versus-Host Disease on the Outcome of Allogeneic Stem Cell Transplantation Recipients Requiring Intensive Care.

BackgroundAdmission of allogeneic stem cell transplantation (SCT) recipients to the intensive care unit (ICU) remains controversial, especially when graft-versus-host disease (GVHD) is present. MethodsWe performed a retrospective study to assess prognostic factors of survival in all allogeneic SCT recipients admitted to the ICU between 2002 and 2013 in our center which has flexible admission criteria, especially regarding GVHD. ResultsOf 349 patients who underwent allogeneic SCT during the study period, 92 patients (26%) were admitted to the ICU. Intensive care unit and hospital discharge rates were 66% and 46%, respectively, whereas 1 year survival was 24%. Acute GVHD, either grade III to IV (30 patients, 33%) or refractory (12 patients, 13%) had a nonsignificant impact on hospital mortality (odds ratio [OR], 2.1; P = 0.1; OR, 5, P = 0.05, respectively). Fifty percent of patients required invasive mechanical ventilation, 30% required vasopressors, 17% required renal replacement therapy, and 28% had liver impairment (bilirubin >34 &mgr;mol/L), each of these parameters defining organ failure. Mortality was closely associated with the number of organ failures as hospital discharge rates were 69%, 50%, 42%, and 0% among patients with 0 (26 patients), 1 (26 patients), 2 (26 patients), and 3 to 4 (14 patients) organ failures, respectively (OR, 2.7; 95% confidence interval, 1.6-4.6; P < 0.001 according to the number of organ failures). ConclusionsEarly mortality of allogeneic SCT recipients admitted to the ICU is especially influenced by the number of organ failures and therefore patients with 0 to 2 organ failures should be considered if required. Refractory GVHD affects survival but not within the confined ICU admission.

The Clinical Picture of Severe Systemic Capillary-leak Syndrome Episodes Requiring Icu Admission

Objective: Systemic capillary-leak syndrome is a very rare cause of recurrent hypovolemic shock. Few data are available on its clinical manifestations, laboratory findings, and outcomes of those patients requiring ICU admission. This study was undertaken to describe the clinical pictures and ICU management of severe systemic capillary-leak syndrome episodes. Design, Setting, Patients: This multicenter retrospective analysis concerned patients entered in the European Clarkson’s disease (EurêClark) Registry and admitted to ICUs between May 1992 and February 2016. Measurements and Main Results: Fifty-nine attacks occurring in 37 patients (male-to-female sex ratio, 1.05; mean ± SD age, 51 ± 11.4 yr) were included. Among 34 patients (91.9%) with monoclonal immunoglobulin G gammopathy, 20 (58.8%) had kappa light chains. ICU-admission hemoglobin and proteinemia were respectively median (interquartile range) 20.2 g/dL (17.9–22 g/dL) and 50 g/L (36.5–58.5 g/L). IV immunoglobulins were infused (IV immunoglobulin) during 15 episodes (25.4%). A compartment syndrome developed during 12 episodes (20.3%). Eleven (18.6%) in-ICU deaths occurred. Bivariable analyses (the 37 patients’ last episodes) retained Sequential Organ-Failure Assessment score greater than 10 (odds ratio, 12.9 [95% CI, 1.2–140]; p = 0.04) and cumulated fluid-therapy volume greater than 10.7 L (odds ratio, 16.8 [1.6–180]; p = 0.02) as independent predictors of hospital mortality. Conclusions: We described the largest cohort of severe systemic capillary-leak syndrome flares requiring ICU admission. High-volume fluid therapy was independently associated with poorer outcomes. IV immunoglobulin use was not associated with improved survival; hence, their use should be considered prudently and needs further evaluation in future studies.

AA amyloidosis as a complication of primary lymphedema.

Abstract Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis. Clinical presentation and age at onset are variable. AA amyloidosis is usually due to chronic inflammatory diseases, malignant tumors or less frequently chronic infectious diseases. We report here the first two cases of AA amyloidosis present with renal failure and nephrotic syndrome in patients with primary lymphedema-induced chronic leg ulcers. The first patient was a 62-year-old female who presented with chronic untreated leg ulcers for 8 years secondary to primary lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of AA amyloidosis. The second patient was a 54-year-old male who presented with hereditary lymphedema and elephantiasis since the age of 12. A salivary gland biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely reported to induce AA amyloidosis. Only five other cases have been reported in the literature, but none of them with chronic lymphedema. We believe that the relation between lymphedema, chronic leg ulcers and AA amyloidosis is underestimated.

Steroid-resistant minimal change nephrotic syndrome in Waldenström macroglobulinemia

Dear Editor, Renal complications of IgM-secreting monoclonal proliferations are rare. Kidney lesions associated with Waldenstrom macroglobulinemia (WM) include mainly intracapillary deposits of IgM with or without cryoglobulinemia, ALamyloidosis and interstitial lymphoplasmatic cell infiltration [1, 2]. Minimal change nephrotic syndrome is a rare complication of WM and has been described, best to our knowledge, only twice in the literature [3, 4]. We herein report a case of WM-associated steroid-resistant nephrotic syndrome due to minimal change lesions. A 67-year-old female was admitted to our department for generalised oedema. Past medical history included WM and anxio-depressive syndrome. WM was diagnosed 2 years ago and necessitated only regular follow-up without any specific treatment; capillary electrophoresis was showing a stable serum monoclonal IgM at 17 g/L. Physical examination on admission confirmed the generalised oedema, weight gain of 6 kg, blood pressure 130/80 mmHg, no hepatosplenomegaly nor lymphadenopathy. Biological tests showed mild acute renal failure with serum creatinine 105 μmol/L (reference 50–90) and severe nephrotic syndrome with hypoalbuminaemia of <10 g/L (35–52) and proteinuria 15 g/day. Her haemoglobin was 11.4 g/dL (12.5–15.5 g/dL); leucocytes, 9.4×10/ L (4–10×10/L), and platelet count, 599×10/L (150–400× 10/L). Capillary electrophoresis showed an increase of serum monoclonal IgM from 17 to 26 g/L, indicating tumour progress. Treatment with high doses of IV furosemide was initiated promptly. Our primary hypothesis was amyloidosis to explain severe nephrotic syndrome in the context of evolving WM. Surprisingly, the renal biopsy (28 glomeruli) showed only minimal change lesions, without amyloidosis or significant interstitial infiltrate (Fig. 1). The immunofixation study showed very mild mesangial IgM deposits. Electron microscopy was not available. Rapidly, the renal function deteriorated with serum creatinine reaching 400 μmol/L. Renal imaging excluded urologic and vascular causes, and particularly, there was no renal vein thrombosis. Most probably, furosemideinduced relative hypovolemia contributed to the aggravating renal failure that has regressed quickly after furosemide dose reduction. We established the diagnosis of WM-associated minimal change nephrotic syndrome (MCNS), and the patient was treated with three pulses of IV methylprednisolone (500 mg/ day) and, subsequently, oral prednisone (1 mg/kg/day) without any response, leading us to reconsider our treatment. Steroids were then withdrawn, and specific WM chemotherapy was started with five courses of rituximab, cyclophosphamide and dexamethasone (RCD). Complete remission of nephrotic syndrome (albumin 36 g/L, proteinuria 0.2 g/day) and significantly improved renal function (serum creatinine 87 μmol/L) were obtained after the third RCD cycle. The renal function was normalised eventually after furosemide J. Sayegh :V. Boisliveau : C. Savary : F. Beloncle : J.-F. Augusto LUNAM Universite, Angers, France

Pseudotumours: an atypical presentation of renal sarcoidosis

### Learning Point for Clinicians Sarcoidosis may present as bilateral kidney pseudotumours. Clinical presentation of this form of renal sarcoidosis is quite unspecific and is usually associated with normal renal function. Its diagnosis relies on imagery [computed tomography (CT) scan] and kidney histology. The literature and the present case suggest the efficiency of corticosteroids. A 32-year-old male was referred to our department for bilateral kidney tumours. Past medical history included sarcoidosis with eyes and lung involvement that was diagnosed 10 years ago and successfully treated with oral corticosteroids for 3 months. Afterwards, he remained asymptomatic until recently when he developed a right renal colic. A CT scan revealed the presence of bilateral renal masses (Figure 1A). Infracentimetric retroperitoneal lymph nodes were detected and their association with the kidney tumours led to suspect the diagnosis of lymphomatous disease and the performance of biopsy of the kidney tumours. The histological analysis showed a granulomatous interstitial nephritis with typical multinucleated giant cells and a surrounding lymphocytic infiltrate. The interstitium was largely replaced by …

Renal Blood Flow and Perfusion Pressure

Abstract The relationship between renal blood flow and renal perfusion pressure is complex. Renal vascularization is autoregulated, meaning that renal blood flow is constant over a broad range of perfusion pressure. A mean arterial pressure higher than the renal lower autoregulation threshold may be considered the most adequate target in patients with shock. However, autoregulation thresholds are not known in humans and may be altered in patients with chronic hypertension and in sepsis. In addition, changes in renal venous pressure observed in certain clinical situations may lead to significant changes in renal perfusion pressure and play a major role in the occurrence of acute kidney injury.