Factor H mutations in hemolytic uremic syndrome cluster in exons 18-20, a domain important for host cell recognition.

Several recent studies have established an association between abnormalities of complement factor H (FH) and the development of hemolytic uremic syndrome (HUS). To identify the relative importance of mutations in FH as a cause of HUS, we have undertaken mutation screening of the FH gene in 19 familial and 31 sporadic patients with FH. Mutations were found in two familial and three sporadic patients, and these clustered in exons 18-20, a domain important for host recognition. Moreover, this study demonstrates that familial HUS is likely to be a heterogeneous condition.

Proximal tubular injury in Chinese herbs nephropathy: monitoring by neutral endopeptidase enzymuria.

Neutral endopeptidase (NEP) is a 94 kDa ectoenzyme of the proximal tubule brush border, physiologically released into the urine with apical membrane fragments. As proximal tubular atrophy was a histological hallmark of Chinese herbs nephropathy (CHN), this study firstly determined renal excretion of NEP in healthy control subjects (N = 31), in patients with CHN (N = 26) and in women having consumed Chinese herbs and whose renal function was normal but running the risk of developing CHN (N = 27). Another patient group consisted of female patients with glomerular diseases (N = 12). At the same time, measurements of urinary microproteins (Clara cell protein, retinol binding protein, beta 2-microglobulin and alpha 1-microglobulin) were performed, as indicators of tubular dysfunction. Cell damage was estimated by the excretion of N-acetyl-beta-D-glucosaminidase (NAG). In the control group, the physiological NEP enzymuria was 43.1 micrograms/24 hr (geometric mean). In CHN patients, levels of urinary NEP were significantly decreased in those with moderate renal failure (26.7 micrograms/24 hr; N = 21; P < 0.05) and almost abolished in end-stage renal failure patients (4.35 micrograms/24 hr; N = 5; P < 0.05). In patients at risk as well as in patients with glomerular diseases, urinary NEP levels were not statistically different from those observed in control subjects (40.68 micrograms/24 hr and 48.5 micrograms/24 hr, respectively). Several degrees of tubular dysfunction and injury were noted in patients groups, as attested by increased urinary microproteins and NAG excretions. Considering the data from control and CHN patients, NEP enzymuria positively correlated with individual creatinine clearance values (r = 0.76; P = 0.0001) and negatively correlated with urinary microproteins levels (r = -0.55; P = 0.00001). Finally, NEP was regularly quantitated in the urine of 6 CHN patients for a period ranging from six months to two years and in 19 patients at risk during two years, respectively. In the first group, renal function progressively deteriorated in 3 patients, leading them to renal replacement therapy after 38 to 115 weeks. Stable parameters were observed in the remaining 3 patients. A direct correlation between creatinine clearance and NEP excretion was found longitudinally in each case. In the second group, no significant change of urinary NEP levels was observed (45.9 micrograms/24 hr), in parallel with stable renal function. Taken together, these results indicate that, in CHN patients, NEP enzymuria provides a rapid and noninvasive determination of the degree of structural impairment affecting the proximal tubular population and further reflecting the severity of the renal disease. The interest of this urinary marker in monitoring the progression of other tubulointerstitial diseases remains to be assessed.

Adhesion molecules and leukocyte common antigen on monocytes and granulocytes during hemodialysis.

As contact of blood with artificial membranes may activate cell adhesiveness, we investigated in 5 patients the expression of several adhesion-promoting molecules on monocytes and granulocytes during hemodialysis on cuprophane (CU), cellulose acetate (CA), and polyacrylonitrile (PAN) membranes. After staining with specific fluorescent monoclonal antibodies, flow cytometric analysis was performed to evaluate the expression of CD11b (= Mac 1, CR3, or C3bi receptor), CD11a (= leukocyte function antigen 1 or LFA-1, or gp 180/95), CD54 (= intercellular adhesion molecule 1 or ICAM 1), and CD45 (= leukocyte common antigen) on circulating leukocytes. Granulocytopenia occurred at 15 minutes with CU and CA but not with PAN; significant monocytopenia occurred on the contrary with all 3 membranes. The drop in monocyte counts was maximal at 15 minutes on CU and CA, and at 180 minutes on PAN; it was also more important with CU (88 +/- 2.6%, alpha = 0.005) and CA (66.4 +/- 4.1%, alpha = 0.01) than with PAN (36.2 +/- 6.2%). Hemodialysis on CU, CA, and PAN was associated with a 2- to 3-fold CD11b and CD45 overexpression on peripheral monocytes; these molecules also increased on circulating granulocytes but to a lesser extent on PAN than on CU and CA (alpha < 0.05). There were no hemodialysis-induced changes in CD11a and CD54 expression on circulating monocytes or granulocytes. The upregulation of CD11b may provide a molecular mechanism for the sequestration of monocytes and granulocytes in the circulation during hemodialysis, while upregulation of CD45 might reflect mechanisms regulating the leukocyte activation state.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical role of iron overload in the increased susceptibility of haemodialysis patients to bacterial infections. Beneficial effects of desferrioxamine.

Iron overload, which is a common complication in haemodialysis patients, is known to enhance bacterial growth and virulence, and to alter phagocytosis. We reviewed the data of 61 haemodialysed patients to clarify the clinical relevance of iron status to the risk of bacterial infection. Increased concentrations of serum ferritin were associated with a greater infection rate (P less than 0.0025), which was already true for ferritin values between 500 and 1000 micrograms/l (P less than 0.025). Furthermore, in 21 iron-overloaded patients treated with an iron-chelator (desferrioxamine), the infection rate decreased from 1/19 patient-months to 1/112 (P less than 0.005), and returned to previous values when desferrioxamine was stopped. Our results demonstrate the importance of haemosiderosis in the increased susceptibility of haemodialysed patients to infections; this susceptibility is decreased by desferrioxamine therapy, which probably acts by restoring phagocytosis and reducing the bioavailability of iron for pathogens.

Renal hematoma in a patient undergoing hemodialysis. Complication of acquired renal cystic disease.

A spontaneous renal hematoma developed in a patient treated by long-term intermittent maintenance hemodialysis. This scanty complication of hemodialysis was related to the recently described acquired cystic disease of the kidneys. Diagnosis was ascertained before nephrectomy by computed tomography and selective renal angiography.