[Classification and therapeutic management of monoclonal gammopathies of renal significance]. / Classification et prise en charge thérapeutique des gammapathies monoclonales de signification rénale.

Two categories of renal disorders associated with monoclonal gammopathies are to be distinguished, according to the characteristics of the underlying B-cell clone. The first group of renal diseases always occurs in the setting of high tumor mass with production of large amounts of monoclonal immunoglobulins. The main complication is the so-called myeloma cast nephropathy, which almost invariably complicates high tumor mass myeloma. The second group includes all renal disorders caused by a monoclonal immunoglobulin secreted by a nonmalignant B-cell clone, and currently referred as a "monoclonal gammopathy of renal significance (MGRS)". This term was introduced to distinguish monoclonal gammopathies that are responsible for the development of kidney damage from those that are truly benign. The spectrum of renal diseases in MGRS is wide and its classification relies on the localization of renal lesions, either glomerular or tubular, and on the pattern of ultrastructural organization of immunoglobulin deposits. Physicochemical characteristics of the pathogenic monoclonal immunoglobulin are probably involved in their propensity to deposit or precipitate in the kidney, as illustrated by the high rate of recurrence of each specific type after kidney transplantation. Early diagnosis and efficient chemotherapy targeting the causal B-cell clone are mandatory to improve renal prognosis and patient survival.

[AL amyloidosis]. / Amylose AL.

AL amyloidosis belongs to the group of conformational diseases. It is the most common type of amyloidosis with an estimated 500 new cases per year in France. It is due to a small and usually indolent plasma cell clone which synthesizes an unstable, misfolded monoclonal immunoglobulin light chain that is prone to aggregate and form amyloid fibrils. Non-invasive biopsy such as abdominal fat aspiration or minor salivary gland biopsy should be performed to confirm the diagnosis and if negative, involved tissues have to be examined. Clinical presentation is very diverse, as AL amyloidosis can affect almost any organ or tissue in the body, other than the brain. The kidney is the most frequent organ involved, whereas heart disease characterized by restrictive cardiomyopathy is the most severe. Early diagnosis, before advanced cardiomyopathy, is essential for improving outcome. The association of alkylating agent and high-dose dexamethasone is effective in almost two-thirds of patients. Combinations of proteasome inhibitors, dexamethasone, and alkylating agents achieve high response rates. Close monitoring of clonal and organ response is mandatory to guide therapy changes and duration. New treatments designed to eliminate amyloid deposits are under development.

[Disseminated arterial occlusions revealing bilateral venous thrombosis with paradoxical embolisms]. / Occlusions artérielles disséminées révélant une thrombose veineuse bilatérale avec embolies paradoxales.

Paradoxical embolism is a diagnosis of exclusion. Clinical triad associates deep venous thrombosis with or without pulmonary embolism, arterial embolism, and intracardiac communication with right-to-left shunt. The intracardiac communication is generally related to a patent foramen ovale (PFO). We report a 75-year-old patient, who presented with bilateral deep venous thrombosis of the legs, complicated by massive pulmonary embolism and paradoxical embolisms through a PFO. This resulted in cerebral, mesenteric, splenic and bilateral kidney infarctions. A promptly initiated anticoagulant treatment allowed a favourable outcome.

[Quinine-induced renal bilateral cortical necrosis]. / Nécrose corticale rénale bilatérale induite par la quinine.

Acute bilateral renal cortical necrosis is a rare cause of renal failure frequently induced by disseminated intravascular coagulation (Dic) following obstetrical complications, sepsis and drugs. We describe a case of Dic with bilateral cortical necrosis after ingestion of only one tablet of quinine. A 41-year-old woman was admitted for severe abdominal pain, melaena, fever and anuria two hours after quinine tablet intake for nocturnal leg cramps. Her medical history included angioneurotic edema caused by chloroquine for malaria prevention. Physical examination was normal. Laboratory data showed acute renal failure, hemolytic anemia without schistocytes and Dic. Platelet antibodies were negative. Ultrasonographic examination showed a complete defect of renal perfusion with permeable renal arteries. Results of abdominal CT scan and MAG3 scintigraphy led to the diagnosis of bilateral renal cortical necrosis. The patient underwent plasma exchanges with fresh frozen plasma which induced rapid resolution of Dic. She remained dependent on chronic hemodialysis. Quinine-induced microangiopathic hemolytic anemia and Dic is a rare described entity. These complications occur typically in quinine-sensitized subjects. The presence of acute renal failure is generally associated with poor prognosis in case of bilateral renal cortical necrosis. Caution is required for the prescription of quinine derivates, which should be avoided in patients experienced on adverse reaction to the drug.

Long-term maintenance of calcineurin inhibitor monotherapy reduces the risk for squamous cell carcinomas after kidney transplantation compared with bi- or tritherapy.

The incidence of skin cancer after organ transplantation is mainly related to type, level, and duration of immunosuppression. The immunosuppressive minimization strategy reduces skin malignancies, but no data are available concerning long-term calcineurin inhibitor (CNI) monotherapy compared with bi- or tritherapy. We studied the benefits of long-term CNI monotherapy (>6 years of exposure) with regard to the incidence of squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) compared with bi- or tritherapy, among first renal allograft adult recipients who were more than 6 years posttransplantation. Among 294 renal transplantations performed between 1986 and 1999, 80 patients received CNI monotherapy (MT) and 86 patients bi- or tritherapy (BTT) with a follow-up of more than 6 years. MT patients were older, had longer follow-up, and fewer biopsy-proven acute rejection episodes. The incidence of SCC was 15.9 SCC/1000 patients/year for MT vs 26.2 for BTT (P = .07). The incidence was significantly lower for patients older than 40 years (22.4 vs 56, respectively; P < .01). The incidence of BCC was 28.3 BCC/1000 patients/year for MT and 10.1 for BTT (P = .05), which failed to show a significant difference in patients older than 40 years (39.7 vs 25, respectively; P = .09). The ratio of SCC/BCC in MT was maintained around 1/2 over time, while it exceeded 2/1 in BTT after 12 years posttransplantation. Patient survival was comparable between the 2 groups. A higher graft survival rate was observed in the MT group. CNI monotherapy should be considered to be a beneficial, safe immunosuppressive minimization strategy for SCC in selected recipients.

Acute immuno-allergic interstitial nephritis caused by fluindione.

Fluindione is a vitamin K antagonist that is commonly prescribed for the treatment of cardiovascular disease and venous thromboembolism in France. Bleeding is the most common side effect of fluindione, whereas hypersensitivity reactions are rare. We describe here a patient with acute immuno-allergic interstitial nephritis caused by fluindione. Initial symptoms included fever, eosinophilia, low albuminuria, microscopic hematuria, eosinophiluria and acute renal failure. Kidney biopsy showed severe interstitial nephritis with interstitial edema, inflammatory infiltrates and tubulorrhexis. Fluindione withdrawal and corticosteroid treatment resulted in rapid recovery of renal function. A review of the literature revealed a very low incidence of fluindione-induced interstitial nephritis, with variable renal and extra-renal signs. Early recognition of this rare complication may prevent the development of severe chronic renal injury.

Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients.

Cytomegalovirus (CMV) seronegative renal allograft recipients (R-), particularly those with a graft from a CMV-seropositive donor (D+), are at high risk for primary CMV infection. CMV resistance to antiviral oral therapy is an emerging problem in renal transplantation, prompting development of new prophylactic strategies. We retrospectively studied the 1-year posttransplantation incidence of CMV infection in high-risk renal transplant recipients, in whom polyvalent intravenous immunoglobulins (IVIg) were used as prophylaxis. Forty R- patients received immunoprophylaxis by polyvalent IVIg (0.25 g/kg weekly for 8 weeks, starting on the operative day). CMV serological tests remained negative in eight patients (20%). Eight patients (20%) had asymptomatic CMV infection while 24 (60%) developed CMV syndrome and were treated with gancyclovir (10 mg/kg/day intravenously for 3 weeks). None had CMV disease or opportunistic infection. Six patients (15%) had biopsy-proven acute rejection, which followed CMV syndrome in three cases. One-year renal allograft and patient survivals were 95% and 97.5%, respectively. Mean serum creatinine level was 124 +/- 33 micromol/L at 1 year. Clinical tolerance of IVIg was excellent, without any episode of acute renal failure. Polyvalent IVIg provides effective prophylaxis in renal transplant recipients at high risk for CMV infection and is associated with excellent 1-year allograft survival. Because of their immunomodulatory functions, IVIg may have a beneficial effect on the incidence of acute and chronic rejection and allograft survival. A randomized prospective study is required to evaluate long-term effects of CMV prophylaxis with polyvalent IVIg compared to antiviral agents in renal transplant recipients.

[An unusual diagnostic of quadriparesia: hyperkalemic paralysis. Report of four non-familial cases]. / Un diagnostic inhabituel de quadriparésie: l'hyperkaliémie paralysante. A propos de quatre cas non familiaux.

INTRODUCTION: The classical cause of hyperkalemic paralysis is the hereditary hyperkalemic paralysis. Very rarely, secondary forms of hyperkalemic paralysis have been reported. EXEGESIS: Four cases of acute paralysis mimicking Guillain-Barre syndrome in three cases and revealing severe hyperkalemia are presented. All the four patients had moderate chronic renal insufficiency. In two cases, the patients received spironolactone. One case was associated with lysis syndrome. All the 4 cases dramatically improved with the treatment of hyperkalemia. CONCLUSION: These cases pointed out the possibility for acute peripheral paralysis to reveal severe hyperkalemia.

Preemptive renal transplantation in adults.

Recent studies have clearly demonstrated that preemptive renal transplantation is associated with better graft and patient survival. It improves the quality of life and is a cost-effective option compared to conventional transplantation. We report our experience with this concept and review the literature. We retrospectively analyzed all adult kidney transplantations performed in our center between March 1986 and May 2004: among 463 renal transplantations 44 were preemptive (9.5%). Mean follow-up was 45.7 +/- 6 months in preemptive versus 62.3 +/- 2.6 months in the other group. At the end of the study, graft survivals were 93.2% and 77.1%, respectively (P = .02). Patient survival rates were similar in both groups. In the preemptive group, grafts were more likely to come from living donors (P < .001) and cold ischemia time was shorter (P = .02). A subgroup case-control study showed that cost saving for dialysis in the preemptive group was about 119,000 Euros per patient. More preemptive patients had professional activity before (P = .0002) and after transplantation (P = .02). Our results and data from the literature support the place of preemptive transplantation as the optimal mode of renal replacement therapy for medical and socioeconomic reasons.

[Immunoglobulin light chain amyloidosis: recent molecular, clinical and therapeutic approach]. / Amylose AL "primitive": aspects physiopathologique, clinique et thérapeutique actuels.

AL amyloidosis is a rare disorder characterised by tissue deposition of a fibrillary proteinaceous material, formed from monoclonal immunoglobulin light (or exceptionally heavy) chains. Although it may complicate multiple myeloma or B-cell lymphomas, AL amyloidosis is often associated with a low burden of clonal plasma cells ("primitive" AL amyloidosis). The mechanisms involved in the formation of AL amyloid deposits remain unclear, but are probably related to structural peculiarities of monoclonal immunoglobulin light chains. AL amyloidosis is usually a systemic disease, often revealed by renal involvement, the most common complication of the disease. The longterm prognosis of AL amyloidosis is poor, mainly related to amyloid restrictive cardiomyopathy leading to congestive heart failure. Oral melphalan and prednisone is considered the standard treatment for AL amyloidosis, but with limited increase in the median survival. High-dose intra-venous melphalan with autologous stem cell transplantation is an effective treatment, aimed at eliminating the clonaly expanded plasma cells, which has been shown to induce complete hematologic remissions and to prolong survival. However, the tolerability of such treatment is low, limiting its use to selected patients. The development of new drugs, able to interfere with amyloid fibril deposition, may provide a new therapeutic approach.