Christian Svalander

Cadmium, mercury, and lead in kidney cortex of the general Swedish population: a study of biopsies from living kidney donors.

Cadmium, mercury, and lead concentrations were determined in deep-frozen kidney cortex biopsies taken from 36 living, healthy Swedish kidney donors (18 males and 18 females), who were 30-71 (mean 53) years of age. Information about occupation, smoking, the presence of dental amalgam, and fish consumption could be obtained for 27 of the donors. The samples (median dry weight 0.74 mg) were analyzed using inductively coupled plasma mass spectrometry, and the results were transformed to wet-weight concentrations. The median kidney Cd was 17 micrograms/g (95% confidence interval, 14-23 micrograms/g), which was similar in males and females. In 10 active smokers, the median kidney Cd was 24 micrograms/g, and in 12 who never smoked, it was 17 micrograms/g. The median kidney Hg was 0.29 micrograms/g, with higher levels in females (median 0.54 micrograms/g) than in males (median 0.16 micrograms/g). Subjects with amalgam fillings had higher kidney Hg (median 0.47 micrograms/g, n = 20) than those without dental amalgam (median 0.15 micrograms;g/g, n = 6), but kidney Hg was below the detection limit in some samples. Nearly half of the samples had kidney Pb below the detection limit. The median kidney Pb was estimated as 0. 14 micrograms/g. This is the first study of heavy metals in kidney cortex of living, healthy subjects, and the results are relatively similar to those of a few previous autopsy studies, indicating that results from autopsy cases are not seriously biased in relation to kidney metal concentrations in the general population. Cd concentrations in those who never smoked were relatively high, indicating considerable Cd intake from the diet in Sweden. The effect of dental amalgam on kidney Hg was as expected, although the reason for the difference in Hg levels between males and females is unclear. ImagesFigure 1

Blood group A and B antigen expression in human kidneys correlated to A1/A2/B, Lewis, and secretor status.

Background. In the revived interest in crossing ABO barriers in organ transplantation renal A/B antigen expression has been correlated with donor ABO, Lewis, and secretor subtype to predict antigen expression. Methods. A/B antigen expression was explored by immunohistochemistry in LD renal biopsies. Donor A1/A2/B, Lewis, and secretor status were determined by serology and polymerase chain reaction. Results. In the renal vascular bed, three distinct A antigen expression patterns with a major, minor, and minimal staining distribution, and intensity (designated as types 3+, 1+ and (+) respectively) were identified. Type 3+ had a strong A antigen expression in the endothelium of arteries, glomerular/peritubular capillaries and veins. The type 1+ showed an overall weaker antigen expression, whereas type (+) had faint staining of peritubular capillaries only. In all cases, distal tubular epithelium was focally stained, whereas proximal tubules were negative. Type 3+ were all from blood group A1 subtype individuals while A2 cases expressed either a 1+ or (+) pattern. The secretor gene did not appear to influence renal A antigen expression. All B kidneys examined showed a B antigen pattern slightly weaker but otherwise similar to A type 3+. Conclusion. Renal vascular A antigen expression correlates to donor A1/A2 subtypes, whereas B individuals show one singular antigen pattern. From antigen perspective, A1 and B donors are a “major” and A2 individuals a “minor” antigen challenge in ABO-incompatible renal transplantation.

ABO‐incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti‐CD20 antibody treatment

Abstract: Background: Blood group ABO‐incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO‐incompatible LD renal transplantation using specific anti‐A/B antibody (Ab) immunoadsorption (IA) and anti‐CD20 monoclonal Ab (mAb) treatment.

Clinical risk factors for recurrence of IgA nephropathy

No clinical risk factors for recurrence of immunoglobulin A (IgA) nephropathy in kidney transplants have been defined. This is a single‐centre retrospect analysis of recurrence in 104 first kidney transplant patients with biopsy‐verified IgA nephropathy. Fifty patients had living donors. All but an identical twin were treated with cyclosporin A. The median follow‐up time was 5 yr. Graft biopsies had been obtained from 35 grafts later than 6 months after transplantation, due to deteriorating graft function or gross proteinuria. Thirteen biopsies showed mesangial glomerulopathy – proliferative in eleven cases – with IgA deposits. Recurrence caused failure of six grafts. Eleven grafts with recurrence were from living donors (p=0.005). No specific human leukocyte antigen (HLA) was identified as a risk factor. Known duration of original disease until end‐stage renal failure was significantly shorter in patients with recurrence (median 5 yr, range 0–25 yr) compared with those without (median of 10 yr, range of 0–37 yr) (p=0.015). Cumulative graft survival was not reduced in living versus cadaveric donor recipients.

Acute Renal Failure after Analgesic Drugs Including Paracetamol (Acetaminophen)

Seven patients with acute renal failure after ingestion of analgesic drug combinations including paracetamol were seen. They presented with oliguric renal failure and restitution of renal function was complete. Only 2 patients had severe liver damage and 2 patients had no signs of liver abnormality. Renal biopsies, studied by light and electron microscopy, in 3 patients showed focal tubular epithelial cell necrosis. Focal vascular damage, predominantly of endothelial cells, was also present in all specimens. This vascular injury was found in various locations in the kidney, including the glomerular and peritubular capillaries and small arterioles. This suggests that microvascular damage is an important mechanism for the renal injury after analgesic drugs.

Renal transplantation in patients with systemic lupus erythematosus: increased risk of early graft loss.

The outcome of primary renal transplantation in 31 SLE patients was evaluated in relation to two contemporary controls per patient, matched for age, sex and immunosuppressive therapy. The proportion of living donors was one third in both groups. Patient survival did not differ, but graft survival at 6 and 12 months post transplantation was significantly reduced in SLE patients (p less than 0.001). When divided into groups using either azathioprine and steroids or combinations including cyclosporin A (14 and 17 SLE patients in each group), graft survival was significantly reduced for the azathioprine-treated SLE patients, 36% vs. 82% for their controls at one year. For cyclosporin-treated SLE patients, one-year graft survival was 59% vs. 85% for their controls, and 6 out of 17 grafts in the cyclosporin-treated group were lost within the first month vs. only 4 out of 34 controls. These differences were, however, not statistically different. Most failed grafts were lost from rejection, with a high proportion of acute vascular rejection, isolated or in combination with cellular rejection. There was no apparent association between rejection and HLA-matched or presence of HLA antibodies. Retransplantation was successful in 6 out of 7 cases. We conclude that SLE patients have an increased risk of early graft rejection, but that this may be overcome by more powerful immunosuppressive therapy.

Beneficial effect of captopril on systemic lupus erythematosus-like disease in MRL lpr/lpr mice

MRL lpr/lpr (MRL/l) mice exhibit a disease similar to systemic lupus erythematosus (SLE) in humans. To investigate the influence of antihypertensive treatment on this disease, four groups of MRL/l mice were treated with the angiotensin-converting enzyme inhibitor captopril (n = 25), with the sympathetic blocker bretylium (n = 15), and with cyclophosphamide (n = 10). Thirty-five mice did not receive any treatment and served as controls. Survival rate, blood pressure, incidence of proteinuria and hematuria, renal pathology, lymphoid hyperplasia and dermatitis were studied. The survival at the age of 36 weeks was significantly improved by captopril as compared to controls (60 vs. 25%, p = 0.035). The cyclophosphamide group showed no mortality at that time and the bretylium group did not differ from the control group. Captopril and bretylium reduced systolic blood pressure significantly while cyclophosphamide was without effect. Captopril and cyclophosphamide diminished significantly the glomerular damage with less proliferative changes and a decreased incidence of proteinuria. The bretylium-treated animals also exhibited an improved renal pathology index but they did not differ from the controls with respect to proteinuria and hematuria. Lymphoid hyperplasia and dermatitis were decreased only by captopril and cyclophosphamide. It is concluded that captopril improves survival in SLE disease of MRL/l mice, counteracting lymphoid hyperplasia, renal disease, dermatitis and decreasing arterial blood pressure.

Adult ABO‐incompatible liver transplantation, using A2 and B donors

Abstract: Background: The longer waiting time for a liver graft in patients with blood group O makes it necessary to expand the donor pool for these patients. This applies in both urgent situations and for elective patients. We report on our experience with ABO‐incompatible liver transplantation using A2 and B non‐secretor donors here.

Cure of zygomycosis caused by a lipase-producing rhizopus rhizopodiformis strain in a renal transplant patient

A 40-year-old man with renal failure due to membranous glomerulonephritis received a cadaveric renal transplant and immunosuppressive therapy with cyclosporine, azathioprine and steroids. Initially the transplantation was successful. 12 days after the transplantation, however, serous secretion appeared in the wound. Later, black necrosis was seen. Fungal culture showed growth of a zygomycete species. Rhizopus rhizopodiformis, with high in-vitro resistance to amphotericin B, flucytosine, fluconazole, ketoconazole and itraconazole. The MIC value for the allylamine derivative SF86-327 (Exoderil) was 1.6 micrograms/ml. Microscopic examination of sections from a surgical revision showed necrosis of the fat tissue and massive hyphal invasion of the perirenal fat, which contained semi-crystalline material anisotropic as seen in polarized light and characteristically staining with rubeanic acid. These histological data indicate a lipase-induced in-vivo splitting of lipids into fatty acids. In-vitro R. rhizopodiformis showed very high extracellular lipase production. 11 days after initiation of amphotericin B therapy cultures and sections remained positive for rhizopus. Amphotericin B was therefore supplemented with Exoderil orally, cyclosporine and steroids were maintained, and azathioprine was discontinued. The wound granulated, shrank, and healed completely in 10 weeks.

Effect of captopril on murine systemic lupus erythematosus disease

The MRL/1 and New Zealand black-New Zealand white cross (NZBxW) mice spontaneously develop a disease similar to systemic lupus erythematosus in man. The effect of antihypertensive treatment on MRL/1 and NZBxW mice was studied with respect to survival, blood pressure, proteinuria, haematuria and renal histopathology. The treatment consisted of angiotensin converting enzyme (ACE) inhibitors (captopril and enalapril) and bretylium, a sympathetic blocker. Tail systolic blood pressure was measured with a strain gauge technique. All antihypertensive drugs caused a reduction in blood pressure in both strains. In MRL/1 bretylium and both ACE inhibitors improved renal histopathology, but only captopril prolonged survival, and it decreased proteinuria and haematuria. In NZBxW captopril decreased proteinuria but did not influence survival or renal histopathology. Bretylium was without any effect on these parameters. At the doses used captopril improves survival in MRL/1 mice and decreases proteinuria and haematuria in both MRL/1 and NZBxW mice. Since bretylium and enalapril lack this property despite a similar blood pressure reduction, it seems to be a drug-specific action.