Light chain deposition disease without glomerular proteinuria: a diagnostic challenge for the nephrologist.

BACKGROUND: Renal involvement in light chain (LC) deposition disease (LCDD) is typically characterized by nodular glomerulosclerosis and nephrotic range proteinuria. Rare cases of LCDD without glomerular symptoms have been reported, but clinical and pathological characteristics of this entity remain poorly described. METHODS: This multi-centre retrospective study included 14 patients with biopsy-proven renal LCDD and proteinuria <0.5 g/day at diagnosis. RESULTS: Baseline median serum creatinine was 281 (136-594) µmol/L, with a glomerular filtration rate of 20 (6-48) mL/min/1.73 m(2). A serum monoclonal immunoglobulin was detected in 12 cases and LC proteinuria only in 7, always of kappa isotype. Monoclonal gammopathy of undetermined significance/indolent multiple myeloma (MM) was diagnosed in nine cases, symptomatic MM in three cases. Hypertension was almost constant (10 of 14). Immunofluorescence studies of kidney biopsies showed linear kappa LC deposition along tubular basement membranes in all cases, with linear glomerular and vascular LC deposits in 11 and 10 patients, respectively. By light microscopy, tubulo-interstitial lesions were prominent in all patients and focal nodular glomerulosclerosis was only observed in two cases. Identification of LCDD led to initiation of chemotherapy in 12 cases. After a median follow-up of 25.5 months, five patients died and four progressed to end-stage renal disease. Renal response occurred in five of the eight patients who achieved sustained haematological response. CONCLUSIONS: LCDD can cause severe renal dysfunction, despite the absence of glomerular symptoms. Early identification of the disease and introduction of a chemotherapy targeting the underlying plasma cell disorder may preserve long-term renal prognosis.

Geographical variability of patient characteristics and treatment patterns affect outcomes for incident hemodialysis patients.

BACKGROUND: Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes. METHODS: Participating countries were grouped according to geographical location; thus study centers in France, Greece, Italy, Portugal and Spain were allocated to southern Europe (n=499), and those in all other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148). Descriptive analysis of patient and treatment patterns at study start, as well as survival analysis, was performed. RESULTS: In patients from the northern European countries, a higher prevalence of diabetes mellitus and of cardiovascular disease was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%, p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p<0.0001). In northern Europe, 23% of patients started hemodialysis with a catheter for vascular access, while in southern European centers, only 13% did so (p=0.0042). Kaplan-Meier survival analysis revealed a lower probability for both all-cause and cardiovascular mortality in southern Europe (log-rank test p<0.001). In a Cox proportional hazards model, a higher mortality risk was estimated for the northern European patients after adjustment for age, sex, membrane permeability, comorbidity index and vascular access (hazard ratio = 1.831; 95% confidence interval, 1.282-2.615; p=0.0009). CONCLUSIONS: Our study patients from northern Europe showed a higher risk profile than those from southern Europe. However, only some of the factors can be modified in attempts to lower the mortality risk in this geographical area.

Comparative outcomes of treated symptomatic versus non-treated asymptomatic high-grade central vein stenoses in the outflow of predominantly dialysis fistulas.

BACKGROUND: Witholding treatment in asymptomatic/pauci-symptomatic high-grade central vein stenosis (CVS), i.e. those not causing debilitating painful extremity oedema, the benefits of which have been shown in only one study in grafts, is debatable. The aim of our study was to assess the short- and long-term benefits of such a strategy in mainly autogenous fistulas. METHODS: We retrospectively compared the outcomes of 53 untreated asymptomatic/pauci-symptomatic and 50 symptomatic high-grade CVS treated by dilation with or without stenting between January 1998 and August 2010 at a single center. Central vein and access patency was estimated by Kaplan-Meier analysis. RESULTS: Mean age, central catheter use and location of stenosis (brachiocephalic vein) in asymptomatic/pauci-symptomatic and symptomatic CVS were significantly different at 69 versus 75 years, 28 versus 48% and 74 versus 56%, respectively. Ninety percent of the cases had an autogenous fistula. The mean degree of stenosis was >80%. Fourty percent of asymptomatic/pauci-symptomatic CVS became severely symptomatic after 4 years. Primary central vein patency at 3, 12, 24 and 36 months in asymptomatic/pauci-symptomatic and symptomatic CVS were 87±5 versus 82±6, 77±6 versus 55±9, 71±7 versus 35±9 and 67±7 versus 18±9%, respectively (P=0.002). Primary access circuit patency rate was not significantly different between the two groups with 66±5 versus 50±4% at 1 year. Secondary central vein and access circuit patency rates at 1 and 3 years were 100 and 93±7 versus 89±5 and 84±7% (P=0.014). CONCLUSIONS: Withholding treatment in asymptomatic/pauci-symptomatic CVS in dialysis fistulas yielded significantly better short- and long-term central vein patency than treatment of symptomatic cases without detrimental effects on overall dialysis circuit.

[Antineutrophil cytoplasmic antibody associated vasculitis in a patient treated with adalimumab for a rheumatoid arthritis]. / Vascularite à anticorps anticytoplasme des polynucléaires neutrophiles chez une patiente traitée par adalimumab pour une polyarthrite rhumatoïde.

Tumor necrosis factor alpha (TNFalpha) plays a central role in the pathogenesis of inflammatory diseases, especially in rheumatoid arthritis, accounting for the increased use of antitumor necrosis factor alpha (anti-TNFalpha) in these disorders. However, these drugs are not devoid of side effects and an increasing number of auto-immune diseases are currently reported. We report an extracapillary and necrotizing glomerulonephritis associated with positive antineutrophil cytoplasmic antimyeloperoxydase antibodies in a 58-year-old woman with a long-standing rheumatoid arthritis treated with adalimumab since four years. Despite the instauration of corticotherapy, cyclophosphamide, plasma exchanges and dialysis, she did not recover her impaired renal function. The link between the vasculitis and adalimumab is not proven, but is highly probable. Vasculitis are more and more reported with anti-TNFalpha therapy but severe renal disease remains exceptional. Pathogenesis probably involves modified immune response with production of autoantibodies. Though anti-TNFalpha treatment is unquestionably indicated in rheumatoid arthritis, we should be aware about the possible link between this treatment and induced vasculitis. Moreover, the use of anti-TNFalpha treatment to manage vasculitis needs to be assessed.