Gabriel Almroth

Plasma exchange or immunoadsorption in patients with rapidly progressive crescentic glomerulonephritis : A Swedish multi-center study

A therapeutic removal of antibodies may be achieved by immunoadsorption (IA) or by plasma exchange (PE). The aim of this prospective randomised study was to compare the efficacy of these different techniques with regard to treatment of patients with rapidly progressive glomerulonephritis (RPG) having at least 50% crescents. Forty-four patients with a RPG were included for treatment either by IA or PE (with albumin as substitution for removed plasma). All patients were additionally treated with immunosuppression. A median of 6 sessions of PEs were performed in 23 patients compared with 6 IAs in 21 patients. Goodpastures syndrome (GP) was present in 6 patients (PE 3, IA 3). All of them started and ended in dialysis, two died. Among the remaining 38 patients (26 men, 12 women) 87% had antibodies to ANCA. Creatinine clearance for PE versus IA were at a median at start 17.1 and 19.8 ml/min, and at 6 months 49 and 49 ml/min, respectively. At 6 months 7 of 10 patients did not need dialysis (remaining: IA 0/5 and PE 2/5, n.s.). The extent of improvement did not differ between the groups. Three patients died during the observation period of 6 months (IA 2; PE 1, on HD). Although no difference was found between the IA or the PE group this study shows that the protocol used was associated with an improved renal function in most patients (except for Goodpastures syndrome) whereas 70% of them could leave the dialysis program.

Autoantibodies to leucocyte antigens in hydralazine‐associated nephritis

Abstract. Clinical and laboratory findings and drug history were studied in 17 patients with suspected hydralazine‐associated nephritis, five of whom only had renal disease, while twelve also had extrarenal manifestations. Renal biopsies revealed extracapillary proliferative or focal segmental proliferative glomerulonephritis in 10 patients, and tubulo‐interstitial nephritis in five patients. Antinuclear antibody (ANA) was found in 16 patients, but none of the 14 patients tested had antibodies to DNA. Tests for antibodies to myeloperoxidase (anti‐MPO) and antibodies to neutrophil cytoplasm antigen (ANCA) were performed by ELISA. Twelve of the 14 patients tested had anti‐MPO; five of these 14 patients had ANCA, while one had borderline levels. These findings suggest that hydralazine facilitates the induction of a systemic disease with multiple autoantibody production.

Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients. A long-term follow up (1989-january 1997)

Abstract. Almroth G, Ekermo B, Månsson A‐S, Svensson G, Widell A. (University Hospital of Linköping; University Hospital of Malmö, Sweden) Detection and prevention of hepatitis C in dialysis patients and renal transplant recipients. A long‐term follow up (1989–January 1997). J Intern Med 2002; 251: 119–128.

Allergic nephropathy associated with norfloxacin and ciprofloxacin therapy : Report of two cases and review of the literature

Allergic nephropathy associated with quinolone antibiotics has been reported in an increasing number of cases. The mechanism might be a hypersensitivity reaction. Norfloxacin has been incriminated previously as a cause once only, with acute interstitial nephritis (AIN) as the histopathological finding. Ciprofloxacin-associated nephropathy has been reported in 28 cases, with AIN as the main histopathological finding. This report describes a second case of AIN associated with norfloxacin treatment and another ciprofloxacin-associated renal interstitial drug adverse reaction. Clinicians should be aware of quinolone-associated AIN, which is a rare but potentially dangerous renal complication.

Serum concentration of interleukin-18 is up-regulated in patients with ANCA-associated vasculitis

We investigated circulating interleukin-18 concentrations in patients with ANCA-associated vasculitis (ASV) and healthy control subjects, and included a group of hemodialysis patients, a patient group previously reported to show high IL-18 plasma levels. Anti-proteinase 3 (PR3) and anti-myeloperoxidase (MPO) serum levels were also measured. Interestingly we found significantly increased serum IL-18 concentrations in ASV patients as compared to healthy controls, 437 vs. 185 pg/ml (p < 0.0001). The increase of IL-18 production was similar irrespective of presence of autoantibodies to PR3 or MPO. As expected the hemodialysis patients also showed significantly increased circulating IL-18 concentrations as compared to control subjects.

Acute glomerulonephritis associated with streptococcus pyogenes with concomitant spread of streptococcus constellatus in four rural families.

We studied history, renal histopathology and microbiology of an epidemic of acute glomerulonephritis associated with throat infections and uncommon culture results in four neighbour families. A 40-year-old man (index patient) was referred to a university hospital for dialysis and kidney biopsy due to a suspected acute glomerulonephritis. An acute tonsillitis had preceded the condition. Penicillin treatment had been started four days before the discovery of renal failure. Throat swabs were positive for β-hemolytic streptococci, group C (GCS). GCS were also found in throat cultures from his wife and two of their children. The bacteria were typed as Streptococcus constellatus. A third child had S. constellatus expressing Lancefield antigen group G. A neighbour and two of his children fell ill the following week with renal involvement. Throat swabs from both these children were positive for S. constellatus. His third child had erythema multiforme and S. constellatus in the throat while a fourth child had β-hemolytic streptococci group A; Streptococcus pyogenes. Kidney biopsies on the index patient and his neighbour showed an acute diffuse prolipherative glomerulonephritis compatible with acute post-streptococcal nephritis and microbiological analysis of renal tissue revealed in both cases S. pyogenes and S. constellatus. The families had had much contact and had consumed unpasteurized milk from our index patients farm. In four of seven persons in two additional neighbouring families S. constellatus was found in throat swabs during the same month while two persons carried Streptococcus anginosus expressing the Lancefield C antigen. In conclusion spread of S. constellatus coincided with the occurrence of four cases of acute glomerulonephritis. The two biopsied patients had both S. pyogenes and S. constellatus present in renal tissue. The epidemic either suggested that the outbreak of glomerulonephritis was due to S. pyogenes but coincided with the transmission and colonization of S. constellatus or that the S. constellatus strains were highly pathogenic or nephritogenic and that this organism can be transmitted in such cases.

Fibroblast Growth Factor 23, Hepatocyte Growth Factor, Interleukin‐6, High‐Sensitivity C‐Reactive Protein and Soluble Urokinase Plasminogen Activator Receptor. Inflammation Markers in Chronic Haemodialysis Patients?

Sera from 84 haemodialysis (HD) patients and 68 healthy blood donors were analysed with commercially available ELISA techniques for fibroblast growth factor 23 (FGF‐23), hepatocyte growth factor (HGF), interleukin‐6 (Il‐6), high‐sensitivity C‐reactive protein (hs‐CRP) and soluble urokinase plasminogen activator receptor (suPAR), to find a possible correlation of FGF‐23 and HGF with the earlier recognized inflammatory markers Il‐6 and hs‐CRP or suPAR. All patients studied had significantly elevated levels of FGF‐23, HGF, hs‐CRP and suPAR as compared to the controls. Il‐6 and hs‐CRP correlated for patients (R = 0.6) as well as for patients and controls altogether. Ln (natural logarithm) of HGF correlated weakly with Ln Il‐6 and Ln CRP (R 0.28–0.37). Ln FGF‐23 correlated only with Ln HGF (r = −0.25) in controls. Ln HGF correlated with ln suPAR (r = 0.6) in both patients and controls. Although elevated as compared to controls, we found no correlation of FGF‐23 with the recognized inflammatory markers Il‐6, hs‐CRP, nor HGF or the new marker suPAR in HD patients. Ln HGF correlated with Ln Il‐6, Ln CRP and Ln suPAR. Although probably involved in vessel disease, FGF‐23 and HGF may play other roles than acting in inflammatory vessel disease in HD patients. Further studies are necessary to evaluate the role of these immunological markers in chronic haemodialysis patients with atherosclerosis.

An Antithrombin III product containing biologically active hepatocyte growth factor may be beneficial in deep ulcer infections

BACKGROUND Widely studied for the past 20 years, hepatocyte growth factor (HGF) has been identified as a regenerative marker and an important factor in the development and healing of injuries. Antithrombin III (AT III) is a protein in the blood stream with anti-thrombotic and anti-inflammatory properties and has been used as an adjuvant treatment along with antibiotics in severe sepsis. OBJECTIVE To study the content and properties of HGF in plasma-derived AT III products, and the regenerative effect in severe deep ulcer infections. METHODS Commercial AT III products were analyzed for the presence and biological activity of HGF. One AT III product containing biologically active HGF was used to treat 18 cases of critical, deep ulcer infections scheduled for major invasive intervention. The patients were followed up for 6-60 months. RESULTS The AT III products contained HGF with different biological activity. No adverse reactions were observed after local administration of AT III during the study or follow-up period. In 16 of 18 cases no surgical intervention was needed within the first 6 month of inclusion. CONCLUSION AT III products containing biologically active HGF may contribute to regeneration and healing in severe deep ulcer infections which do not respond adequately to different combinations of antibiotics alone.

Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders

Background: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce. Design: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients). Results: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönleins purpura had elevated IgA-antibodies to tissue transglutaminase. Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I). One patient with chronic glomerulnephritis also had Marsh I. Conclusions: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.

Serum immunoglobulins and IgG subclasses in patients with glomerulonephritis

Abstract. The serum concentrations of IgG, IgA, IgM and of the four subclasses of IgG were determined by radial immunodiffusion in 103 patients, mean age 42 (range 16–72), with various types of glomerulonephritis. Forty‐nine healthy blood donors, mean age 41 years (range 19–65), served as controls. Kidney biopsies were obtained from all the patients for examination by histopathology and by immunofluorescence. The glomerulopathies were classified according to WHO criteria.