Adequacy targets can be met in anuric patients by automated peritoneal dialysis: baseline data from EAPOS.

OBJECTIVE: Conventional continuous ambulatory peritoneal dialysis (CAPD) in patients without residual renal function and with high solute transport is associated with worse clinical outcomes. Automated peritoneal dialysis (APD) has the potential to improve both solute clearance and ultrafiltration in these circumstances, but its efficacy as a treatment modality is unknown. The European Automated Peritoneal Dialysis Outcomes Study (EAPOS) is a 2-year, prospective, European multicenter study designed to determine APD feasibility and clinical outcomes in anuric patients. The present article describes the baseline data for patients recruited into the study. DESIGN: All PD patients treated in the participating centers were screened for inclusion criteria [urinary output < 100 mL/24 h, or residual renal function (RRF) < 1 mL/min, or both]. After enrollment, changes were made to the dialysis prescription to achieve a weekly creatinine clearance above 60 L per 1.73 m2 and an ultrafiltration rate above 750 mL in 24 hours. SETTING: The study is being conducted in 26 dialysis centers in 13 European countries. BASELINE DATA COLLECTION: The information collected includes patient demographics, dialysis prescription, achieved weekly creatinine clearance, and 24-hour ultrafiltration (UF). RESULTS: The study enrolled 177 anuric patients. Median dialysis duration before enrollment was 22.5 months (range: 0-285 months). Mean solute transport measured as the dialysate-to-plasma ratio of creatinine (D/P(Cr)) was 0.74 +/- 0.12. Patients received APD for a median of 9.0 hours overnight (range: 7-12 hours) using a median of 11.0 L of fluid (range: 6-28.75 L). Median daytime volume was 4.0 L (range: 0.0-9.0 L). Tidal dialysis was used in 26 patients, and icodextrin in 86 patients. At baseline, before treatment optimization, the weekly mean total creatinine clearance was 65.2 +/- 14.4 L/1.73 m2, with 105 patients (60%) achieving the target of more than 60 L/1.73 m2. At baseline, 81% of patients with high transport, 69% with high-average transport, and 40% with low-average transport met the target. At baseline, 70% of patients with a body surface area (BSA) below 1.7 m2, 60% with a BSA of 1.7-2.0 m2, and 56% with a BSA above 2.0 m2 achieved 60 L/1.73 m2 weekly. Median UF was 1090 mL/24 h, and 75% of patients achieved the UF target of more than 750 mL/24 h. CONCLUSION: This baseline analysis of anuric patients recruited into the EAPOS study demonstrates that a high proportion of anuric patients on APD can achieve dialysis and ultrafiltration targets using a variety of regimes. This 2-year follow-up study aims to optimize APD prescription to reach predefined clearance and ultrafiltration targets, and to observe the resulting clinical outcomes.

Pathophysiology of cardiovascular disease in hemodialysis patients.

Cardiovascular disease is the principal cause of morbidity and mortality in dialysis patients. The principal alterations responsible are left ventricular hypertrophy and arterial disease characterized by an enlargement and hypertrophy of arteries and the high prevalence of atheromatous plaques. Left ventricular hypertrophy is the consequence of combined effects of chronic hemodynamic overload and nonhemodynamic biochemical and neurohumoral factors characteristic of uremia. The hemodynamic overload is due to flow and pressure overload. The flow overload is tightly related to hyperkinetic circulation caused by anemia, arteriovenous fistula, or overhydration and is characterized by an enlargement of the left ventricular cavity. The pressure overload in these patients is more tightly related to abnormal geometry and function of large conduit arteries, principally the stiffening of arterial tree. The flow overload is also in large part responsible for remodeling of arterial tree, and as the heart and vessels are a coupled interactive physiological system, cardiac and vascular alterations occur in parallel, being induced to a great extent by the same hemodynamic abnormalities. The principal clinical consequences of left ventricular hypertrophy and arterial alterations are heart failure, ischemic heart disease, and peripheral artery disease. Cardiovascular alterations are only partly reversible, and efforts should be directed toward early prevention.

Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients.

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.

Primary bilateral B-cell renal lymphoma: a case report and review of the literature.

Renal lymphoma is commonly secondary to lymphomatous infiltration of the kidneys in disseminated lymphoma and advanced stage IV disease. We describe a 57-year-old white woman presenting with an acute renal failure due to a bilateral "primary" B-cell lymphoma infiltration of the kidneys. The diagnosis of the lymphoma was made by renal biopsy. The striking feature observed was a destructive infiltration of the kidney by a malignant B-cell lymphoma that left the renal capsule intact, without any sign of secondary localization on the hilar regions. Physical examination did not reveal any peripheral lymphadenopathy or hepatosplenomegaly. A bilateral infiltration of both kidneys was the only feature shown by computed tomography and renal angiography. This case raises the question of the occurrence of a primary B-cell lymphoma in a nonlymphoid organ, which was diagnosed by renal biopsy at a time when the development was exclusively renal in origin.

Cellular immunity in interstitial nephropathy.

Inflammatory tubulointerstitial nephritis (TIN), either as a primary or as a secondary event, plays an essential role in the development of all forms of chronic renal failure. Experimental models of TIN should help in understanding TIN in humans. As in experimental glomerulopathies, the target antigen can be a kidney structural antigen, from the tubular basement membrane (TBM) or not, or a foreign antigen. While some models are due to deposits of free antibodies or circulating immune complexes, many others involve cell-mediated immunity. This last aspect explains the importance and the originality of experimental TIN.

Immunotactoid glomerulopathy and cutaneous vasculitis.

A 22-year-old woman presented glomerulonephritis with Schönlein-Henoch-like syndrome and monoclonal abnormality. One month later, she developed a rapidly progressive glomerulonephritis with hypertension and persistent purpura. In the two renal biopsies performed during the first and the second attack, mesangial expansion and thickening of the glomerular capillary walls (associated with 50% of crescents in the second biopsy) were observed on light microscopy. By immunofluorescence faint deposits of immunoglobulins (light and heavy chains) and complement components were found present in the mesangium. Electron microscopy showed tubular microfibrils measuring 19-24 nm in the mesangium, subendothelial and subepithelial areas. A skin biopsy performed during the first attack demonstrated leukocytoclastic skin vasculitis. By immunofluorescence, no deposits were observed. Congo red staining for amyloid and cryoglobulinemia were negative. This case is similar to an entity recently described and named immunotactoid glomerulopathy.

[Serum lipase and amylase levels in chronic renal failure: interpretation of results--effects of extrarenal purification]. / La lipasémie et l'amylasémie au cours de l'insuffisance rénale chronique: interprétation des résultats--effets de l'épuration extra-rénale.

Serum amylase and lipase activities were studied in two groups of patients without clinical evidence of pancreatitis: 47 with stable chronic renal failure, 61 treated by haemodialysis. Amylase activity was significantly increased in 73 of 108 patients (68%) and lipase activity in 67 of 108 (62%). After dialysis, both enzymatic activities were decreased, despite of the lack of extraction by the artificial kidney. Laboratory confirmation of the diagnosis of pancreatitis is difficult in patients with chronic renal failure, and cannot be supported only by serum amylase and lipase activity measurements.