Proteinuria in early childhood due to familial LCAT deficiency caused by loss of a disulfide bond in lecithin:cholesterol acyl transferase.

INTRODUCTION: Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare recessive disorder of cholesterol metabolism characterized by the absence of high density lipoprotein (HDL) and the triad of corneal opacification, hemolytic anemia and glomerulopathy. PATIENTS: We here report on FLD in three siblings of a kindred of Moroccan descent with HDL deficiency. In all cases (17, 12 and 3 years of age) corneal opacification and proteinuria were observed. In the 17-year-old female proband, anemia with target cells was observed. RESULTS: Homozygosity for a mutation in LCAT resulted in the exchange of cysteine to tyrosine at position 337, disrupting the second disulfide bond in LCAT. LCAT protein and activity were undetectable in the patients' plasma and in media of COS7 cells transfected with an expression vector with mutant LCAT cDNA. Upon treatment with an ACE inhibitor and a thiazide diuretic, proteinuria in the proband decreased from 6g to 2g/24h. CONCLUSION: This is the first report that FLD can cause nephropathy at a very early age.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

Renal failure due to acute phosphate nephropathy.

Case report of a 62-year-old woman who developed acute renal failure due to nephrocalcinosis, also called acute phosphate nephropathy, after large bowel cleansing in preparation for colonoscopy using oral sodium phosphate solution (Phosphoral, de Witt, Cheshire, UK). Subsequently her renal insufficiency resolved only partially resulting in stage 4 chronic kidney disease. In retrospect multiple risk factors for this condition (hypertension, diuretics, AT-II receptor blocker, female gender, advanced age and volume depleting due to vomiting and nausea) were identified. If these factors had been taken into consideration prior to prescribing this drug, acute and chronic renal failure would have been prevented. Future investigation of potential risk factors and the exact mechanism of this complication is necessary to identify those patients prone to develop this complication. In the meantime prescribing physicians should be made aware of this complication. On the basis of the current state of knowledge the evidence seems to be quite compelling not to prescribe these drugs in patients with one or more associated risk factors. It could even be argued that these drugs should not be prescribed at all.

Acute effects of hemodialysis on salivary flow rate and composition.

AIMS: To evaluate acute effects of hemodialysis (HD) on the salivary flow rate, pH and biochemical composition before, during and after completion of a dialysis session. MATERIAL AND METHODS: Unstimulated whole saliva (UWS) and chewing-stimulated whole saliva (CH-SWS) were collected in 94 HD patients. Salivary flow rate, pH, concentrations of total protein, albumin, cystatin C, secretory immunoglobulin A (S-IgA) and of sodium, potassium and urea were measured. RESULTS: HD had an acute stimulating effect on the salivary flow rate (UWSbefore = 0.30+/-0.22 ml/min, UWSduring = 0.39+/-0.25 ml/min, p < 0.005). The mean pH of UWS showed a small but significant increase during HD mainly due to an increased watery secretion from the salivary glands. The salivary biochemical constituents changed markedly, but no significant difference in output was found. The electrolyte concentration did not change significantly during dialysis. The level of urea in CH-SWS declined to 40% (Ureabefore = 25.+/-6.4 mmol/l, Ureaduring = 15.3+/-4.5 mmol/1). CONCLUSIONS: This study shows that HD has significant acute effects on both salivary secretion rate and protein concentrations in saliva. We conclude that the observed changes in salivary concentrations and proteins are mainly due to an increased watery secretion from the salivary glands.

Impaired response rates, but satisfying protection rates to influenza vaccination in dialysis patients.

Dialysis patients show impaired responses to several vaccines. Limited recent data are available on influenza vaccination in these patients. In the 1998-1999 influenza season, 44 dialysis patients received a standard trivalent vaccination followed by a booster two months later. The serum antibody responses in these patients were compared with those found in healthy subjects. A fourfold rise in serum hemagglutination inhibition titre was achieved in 23-58% of all patients. Protective titres were reached in 53-93% of the patients. Since protective antibody titers can be induced, it is recommended to vaccinate dialysis patients annually against influenza.

Intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a rare disease occurring mainly during the last trimester of pregnancy. Pruritus, often accompanied by excoriation of the skin but without other skin lesions, and elevated concentrations of bile acids are characteristic for this disorder. We present a 30-year-old woman with pruritus, elevated bile acids, ASAT and ALAT in the 22nd week of pregnancy. Treatment with ursodeoxycholic acid resulted in complete disappearance of the pruritus and normalisation of the bile acids, ASAT and ALAT. A healthy child was born at term. In the differential diagnosis of liver function abnormalities during pregnancy, ICP should be included. ICP responds very well to treatment with ursodeoxycholic acid, with no detrimental effects for mother and child.

Giant cell myocarditis: a fatal cause of dyspnea in pregnancy.

The clinical course of a pregnant patient, who presented with progressive dyspnea and heart failure is described. Despite intensive care and resuscitative efforts to mother and child, both expired. The autopsy revealed giant cell myocarditis in the mother. Giant cell myocarditis can affect pregnant patients and should therefore be considered in the differential diagnosis of progressive dyspnea.

[Campylobacter infections in pregnancy]. / Campylobacter-infecties in de zwangerschap.

In two pregnant women aged 39 and 35, who presented with fever and diarrhoea, Campylobacter was cultured from a blood sample. They were treated with antibiotics. One had a healthy neonate, in the other intrauterine foetal death had occurred. Campylobacter species have increasingly been recognized as possible causes of septic abortion, premature labour and neonatal sepsis. Early recognition and treatment of maternal Campylobacter infection may reduce the risk of serious foetal or neonatal complications.

Analysis of donor selection procedure in 139 living-related kidney donors and follow-up results for donors and recipients.

In 1981 an active programme was started in our centre for living-related kidney donation (LRD). The structure of this LRD programme is described in this paper. Retrospectively the results of this LRD programme were studied. Between 1981 and 1988 139 potential living donors were evaluated. Of all potential donors 47 (34%) actually donated a kidney, including 24 HLA non-identical combinations. Follow-up was obtained until 1990. An acceptable incidence of morbidity and mortality for donors and recipients was observed. A high number of potential donors was excluded during the selection procedure (66%). They were often refused for medical reasons (29%), with a high incidence of renal dysfunction (16%). No long-term adverse effects of nephrectomy regarding decreased renal function, hypertension, or proteinuria were seen. Of all actual donors 23% experienced minor complications after donation. Living-related kidney transplants showed better graft function than cadaveric grafts.

[Measurement of the quality of care for surgical patients in an intensive care unit in a peripheral hospital]. / Meting van de kwaliteit van de zorg voor chirurgiepatiënten op een intensive care-afdeling in een perifeer ziekenhuis.

OBJECTIVE: To determine the quality of care in an intensive care unit. DESIGN: Prospective investigation for one year. Comparison with results from the literature. SETTING: Surgical intensive care unit of a community hospital. PATIENTS: Measurement of the APACHE-II-score was performed on days 1, 3 and 7 in all surgical intensive care unit patients admitted during a one-year period. The predicted mortality from the literature was compared with the actual mortality in our hospital. RESULTS: A total of 301 patients were admitted to the intensive care unit. Overall mortality was 9%. All the patients with an APACHE II score above 25 on admission died. The actual mortality was comparable with the predicted mortality from the literature. CONCLUSION: The APACHE II score can be used to determine the quality of care in an intensive care unit. Early prediction of a bad prognosis makes transportation to a more specialized hospital possible, before irreversible organ damage develops.

Campylobacter pylori: prevalence and significance in patients with chronic renal failure.

Since gastric symptoms are frequent in uremic patients, we have studied the prevalence and significance of Campylobacter pylori infection in patients with chronic renal failure. The prevalence of serum IgG antibodies to C. pylori in 50 patients on regular dialysis treatment (44%) was similar to that of a control group of 40 blood donors (45%), but was significantly lower (p = 0.0001) than that in 31 patients with peptic ulcer disease (93%). Furthermore, 11 of the 50 patients with chronic renal failure and a history of documented peptic ulcer disease had a similar prevalence of antibodies to C. pylori (45%) as did the 39 chronic renal failure patients without previous peptic ulcer (44%), which was significantly lower (p less than 0.01) than that in the control group of peptic ulcer patients (93%). Of 10 patients with chronic renal failure (6 with and 4 without gastric complaints) studied by endoscopical biopsies, two had chronic active antral gastritis and were positive for C. pylori by histology, culture and had IgG antibodies in their sera, while one patient with normal antral mucosa had IgG antibodies but was negative by culture and histology. Thus, this study shows that there is no predisposition to C. pylori infection among patients with chronic renal failure, and that C. pylori infection does not play a significant role in the ulcer diathesis in these patients.

Measurement of specific IgE antibodies in individuals exposed to formaldehyde.

Using an in-vitro test, the presence of formaldehyde-specific IgE antibodies was investigated in sera from four groups of individuals exposed to formaldehyde by different routes and concentrations. Group (A) 28 subjects living or working in rooms or places where formaldehyde-containing construction materials were used; (B) 18 subjects occupationally exposed to relatively high concentrations of formaldehyde; (C) 12 paramedic employees working in a renal dialysis unit where formaldehyde-sterilized dialysers were being used; and (D) 28 subjects undergoing haemodialysis with these formaldehyde-sterilized dialysers. Formaldehyde-specific IgE antibodies could be detected in only one of the 86 serum samples. This particular sample was from a worker occupationally exposed to formaldehyde (group (B], but who did not show any work-related symptoms. In two pools of control sera from unexposed subjects no specific IgE antibodies to formaldehyde were detected. It is concluded that exposure to formaldehyde, even in relatively high concentrations, rarely evokes the production of specific IgE antibodies. The presence of these specific antibodies is not necessarily attended by allergic symptoms. On the other hand, the symptoms supposed to be related to formaldehyde exposure and reported in this study by 24 out of 28 subjects in group (A), and some of the subjects in groups (B) and (C), cannot be attributed to an IgE-mediated sensitization to formaldehyde.

Composition of IgA-containing circulating immune complexes in IgA nephropathy.

Macromolecular IgA is found with a relatively high frequency in the sera of patients with IgA nephropathy (IgAN). This macromolecular IgA consists of polymeric IgA, IgA-containing immune complexes, or both. The presence of polymeric IgA antibodies reflects a recent IgA response. Vaccination data in patients with IgAN suggest that these patients respond more vigorously with their mucosal immune system than do controls. The association of exacerbations with upper respiratory tract infections suggests that the immunogenic stimuli probably are of microbial origin and are presented to mucosal surfaces. Analysis by sucrose density ultracentrifugation has shown that the macromolecular IgA may contain IgG, IgA rheumatoid factor, and C3. The search for the antigen or antigens specifically responsible for IgAN has been unsuccessful. Although IgG and IgA rheumatoid factor may contribute, they do not account for the pathogenesis of the disease in all patients. Alternative mechanisms have to be assumed for patients who do not have detectable levels of IgA-containing immune complexes. They could have polymeric IgA or IgA-containing immune complexes intermittently, as has been shown in children with relapsing IgAN. The binding of circulating IgA antibodies to antigens present in the mesangium can lead to the local formation of deposits in the absence of circulating IgA complexes.

Circulating IgA immune complexes and skin IgA deposits in liver disease. Relation to liver histopathology.

Alcoholic liver disease (ALD) is characterized by elevated serum IgA concentrations, the presence of circulating immune complexes containing IgA, and IgA deposits along sinusoids in the liver. When combined with the presupposed IgA-clearance function of the liver, a causal association between IgA abnormalities and the liver disease in ALD can be suggested. This prompted us to study the presence and concentration of circulating IgA-containing immune complexes (IgA-CIC) in 41 patients with ALD and 41 patients with other nonalcoholic liver diseases having comparable serum IgA levels. We searched for relationships among IgA-CIC and history of alcohol abuse, liver histopathology, and IgA deposits in the liver. Using an anti-IgA inhibition binding assay, 56% of the patients exhibited IgA-CIC in polyethylene glycol precipitate of serum and 38% showed IgA-CIC in whole serum. The prevalence and concentration of IgA-CIC was lowest in cases with nonspecific changes or steatosis in the liver biopsy and highest in cases with hepatitis or cirrhosis (P less than 0.01). The occurrence of IgA-CIC was not related to a history of alcohol abuse or to the presence of IgA deposits along hepatic sinusoids (which occurred in 78% of ALD and 20% of non-ALD cases). A skin biopsy was available from 34 patients (19 with ALD and 15 with non-ALD). In 68% of these biopsies, IgA deposits were observed in superficial blood capillaries.(ABSTRACT TRUNCATED AT 250 WORDS)

The bone marrow as production site of the IgA deposited in the kidneys of patients with IgA nephropathy.

Patients with primary IgA nephropathy have increased plasma levels of polymeric IgA1 and deposits of IgA1 in their kidneys. The origin of this material is unknown. The production of IgA and its subclasses was investigated in the bone marrow of 14 patients and 19 controls using two colour immunofluorescence and tissue culture. Patients had an increase in the percentage of plasma cells containing IgA (45.8 +/- 7.2 mean +/- s.d.) compared to controls (40.1 +/- 10.5) (P = 0.08). IgA plasma cells containing subclass IgA1 were significantly (P less than 0.01) increased in patients (89.9 +/- 2.7%) compared to controls (84.1 +/- 6.7%). Correspondingly IgA plasma cells containing subclass IgA2 were significantly decreased (P less than 0.01) in patients (7.4 +/- 3.0%) compared to controls (13.5 +/- 5.9%). Production of IgA in bone marrow culture in patients was increased (1,684 +/- 1,151 ng/culture) compared to controls (1,087 +/- 937), but this difference was not significant (P = 0.2). However, in patients the IgA1 subclass contributed significantly (P less than 0.01) more to the IgA synthesis in culture (ratio of IgA1 over IgA: 0.96 +/- 0.02) than in controls (ratio 0.90 +/- 0.06). These findings suggest that the bone marrow may well be the site of long-term overproduction of the IgA1 found in the circulation and mesangial deposits in IgA nephropathy.