Assessing the relative impact of lupus nephritis on mortality in a population-based systemic lupus erythematosus cohort.

OBJECTIVE: There is limited knowledge on the relative impact of lupus nephritis (LN) on morbidity and mortality in population-based systemic lupus erythematous (SLE) cohorts. Here, the primary aim was to compare mortality rates between patients with and without LN in a population-based SLE cohort. METHODS: The study cohort included all SLE patients resident in the city of Oslo during 1999-2008. Follow-up time was median 14 (0-15) years. Presence of LN was defined according to the 1987 American College of Rheumatology classification criteria for SLE. LN class was determined by renal biopsy. Data on kidney function, including presence of end-stage renal disease (ESRD), were obtained from patient charts. Standardized mortality ratios (SMRs) were estimated by comparing deaths in the SLE cohort with age- and gender-matched population controls. RESULTS: We found that 98/325 SLE patients (30%) developed LN, 92% of whom had occurrence within the first five years from disease onset. Incidence rate of ESRD was 2.3 per 1000 patient-years. A total of 56 deaths occurred during the study period, corresponding to an overall SMR in the SLE cohort of 2.1 (95% confidence interval (CI) 1.2-3.4). Estimated SMR for LN patients was 3.8 (95% CI 2.1-6.2), and for SLE patients without LN it was 1.7 (95% CI 0.9-2.7). CONCLUSION: In this population-based SLE cohort, we found that LN was associated with increased morbidity and mortality, whereas SLE patients who did not develop LN had good overall prognoses regarding survival.

Calcineurin inhibitor-free immunosuppression in renal allograft recipients with thrombotic microangiopathy/hemolytic uremic syndrome.

Thrombotic microangiopathy (TMA) and hemolytic uremic syndrome (HUS) represent serious threats to kidney allograft recipients. During a 4-year period, among 850 kidney transplantations, seven recipients with primary HUS and seven recipients (eight transplants) with previous or de novo TMA/HUS were identified and given calcineurin inhibitor (CNI)-free immunosuppression by sirolimus (SRL), mycophenolate mofetil and steroids. Thirteen out of 15 transplantations were successful in the long term; resulting in a mean creatinine of 101 mumol/L (16.4 months follow-up). In patients maintained on CNI-free regimen, no TMA/HUS recurrences were observed. A high rate of acute rejections (53%) may indicate insufficient immunosuppressive power and/or a causative relationship between TMA/HUS and rejection. Wound-related complications were abundant (60%), and call for surgical/immunosuppressive countermeasures. Our experience supports the idea that CNI's are major offenders in TMA/HUS induction. Total CNI elimination seems essential, as the nephrotoxic combination CNI + SRL may promote TMA. Features of TMA/HUS should be carefully explored in recurrent 'high responders'.

[Lupus nephritis with crystal structures in glomerulopathy ]. / Lupusnephritis mit Kristallstrukturen in glomerulären Ablagerungen.

Lupus nephritis is a common phenomenon in Systemic Lupus Erythematosus (SLE). We analyzed a renal biopsy of a 30-year-old woman with SLE. The clinical history showed a typical SLE with generalized symptoms without demonstrable lupus coagulant, positive for anti-nuclear antibodies and anti-ds-DNA antibodies but negative for rheumatoid factor, cryoglobulins and antiphospholipid antibodies. A paraproteinemia for IgA, IgG and IgM was not detectable. Using light, electron and immunoelectron microscopy electron-dense deposits were noted in subepithelial, subendothelial and mesangial position. Most remarkably, the electron-dense deposits and mesangial areas in the vicinity of deposits contained an electron-dense crystalline material. The crystalline structures were composed of IgG and kappa light chains, while they were negative for IgM, IgA and lambda light chains, as demonstrated by immunoelectron microscopy. As far as we know, this is the first case of lupus nephritis with crystalline structures. Since we could not detect cryoglobulinemia or paraproteinemia, other mechanisms possibly favor organization of macromolecular structures.

Varicella infection in a renal transplant recipient associated with abdominal pain, hepatitis, and glomerulonephritis.

A 36-year-old renal transplant patient developed 9 years after a successful transplantation a fatal secondary varicella infection. The disseminated varicella infection was associated with hepatitis with liver necrosis, disseminated intravascular coagulation and fibrinolysis and glomerulonephritis. To our knowledge this is the first description of glomerulonephritis associated with varicella infection in a renal transplanted patient. The autopsy showed morphologically a mesangial glomerulonephritis with minor proliferative activity and extensive deposits by electronmicroscopy, mainly in the mesangium. The ongoing immunosuppression may have modified the mesangial cell response to the deposition of immune complexes.

[South American blastomycosis--a differential diagnosis to tuberculous meningitis]. / Søramerikansk blastomykose--en differensialdiagnose til tuberkuløs hjernehinnebetennelse.

BACKGROUND: South American blastomycosis is primarily a lung infection often complicated by multiorgan or intracranial disease. MATERIAL AND METHODS: We describe the clinical and pathological findings of fatal cerebral blastomycosis occurring in a woman that immigrated to Norway from Brazil 23 years earlier. RESULTS: The clinical symptoms together with the radiological findings of multiple cerebral lesions and thickening of the basal meninges were interpreted as cerebral tuberculosis. Examination of cerebral spinal fluid was inconclusive. A diagnosis of cerebral fungal infection was subsequently established by brain biopsy. INTERPRETATION: This case history stresses the importance of confirming a clinical diagnosis by brain biopsy and extended investigation of the cerebrospinal fluid when intracranial lesions may have an infectious origin.

Carcinoma of the ovary with primary presentation in the choroid.

PURPOSE: An unusual case of choroidal metastases from an ovarian adenocarcinoma is described, and a brief review of the literature is presented. METHODS: Clinical and autopsy findings are presented. RESULTS: After having diagnosed bilateral choroidal metastatic lesions, a clinical investigation and a subsequent laparotomy disclosed bilateral ovarian tumors with histopathological features of mucinous adenocarcinoma. At autopsy the tumor was confirmed to be a primary ovarian mucinous adenocarcinoma with choroidal metastases. CONCLUSION: This article describes what is believed to be the first case report of a primary epithelial carcinoma of the ovary with histopathologically documented metastases to the choroid. Metastatic disease must be considered in the evaluation of patients with choroidal lesions of unknown etiology.

A new immunoelectron microscopy approach for the detection of immunoglobulin and complement deposits in epoxy-embedded renal biopsies.

The purpose of this study was to examine the diagnostic value of a new immunoelectron microscopy technique (IEM) for detection of immunoglobulin and complement deposits in epoxy-embedded renal biopsies. Twenty-four renal biopsies were embedded in epoxy resin following a tissue processing involving moderately increased amount of accelerator, DMP-30 (Tri(Dimethyl Amino Methyl) Phenol), in the infiltration steps. Following antigen retrieval by heating in citrate buffer, immunogold labeling was performed on ultrathin sections from these epoxy blocks with antibodies against immunoglobulins and complement. The sections were counterstained with urnayl acetate and lead citrate without any enhancing procedures. The preservation of the ultrastructure with this method was similar to that usually seen in epoxy embedded material. The immunogold labeling was intense and distinct. Immunofluorescence (IF) for light microscopy was carried out on frozen sections of parallel tissue samples. The correspondence between IF and IEM were good, but in some cases higher sensitivity for IgA with IEM than IF was observed in the sense that smaller amounts of antigen were detectable with IEM. The combination of moderately increased amount of accelerator and antigen retrieval is superior to previous methods with respect to ease of use, ultrastructural preservation, and intensity of the immunolabeling. Moreover, the renal tissue can be processed in an automatic ultraprocessor together with other specimens which are to be prepared for routine electron microscopy.

Immunoelectron microscopy on epoxy sections without deplasticizing to detect glomerular immunoglobulin and complement deposits in renal diseases.

Twenty renal biopsies were studied by immunoelectron microscopy (IEM) after embedding in epoxy resin. Immunogold labeling for immunoglobulins and complement C3 was performed on the epoxy sections, which were not subjected to any kind of etching or deplasticizing prior to the immunolabeling. The concentration of accelerator, DMP-30 (Tri (Dimethyl Amino Methyl) Phenol), was increased in the infiltration and embedding steps far beyond the values normally used to make immunolabeling of these antigens possible on epoxy sections. The sections were stained with tannic acid accompanied by uranyl acetate and lead citrate. Immunofluorescence (IF) for light microscopy was carried out on frozen sections of parallel tissue samples. Some cases with IgA-nephritis demonstrated a higher sensitivity for IEM than IF, in the sense that smaller amounts of antigen were detectable with IEM. Ultrastructural preservation with this method was approximately the same as that usually seen on epoxy-embedded material. By combining excellent immunolabeling with nearly optimal ultrastructural morphology in one procedure, this method is useful particularly in situations where the material available is limited, such as in studies of renal biopsies. As far as we know, this is the first time that immunoglobulins have been satisfactorily immunolabeled on epoxy sections without etching or deplasticizing.

High incidence and aggressive growth of non-AIDS-defining cancers among AIDS patients in Oslo.

The spectrum of cancers advanced by AIDS is disputed. To supplement the register-based investigations, we have studied the occurrence of non-AIDS-defining malignancies in a closely followed population of AIDS patients. The population comprises 255 patients fulfilling CDC's clinical AIDS definition, representing 91% of all adult AIDS patients from Oslo 1983-1995. Full autopsy was performed on 73% of the 211 fatal cases. Adding patients with CD4 cell counts below 200 cells/mm3 to match the US AIDS definition, the population increases to 344, including 225 deceased. The expected number of cancer cases was calculated from age- and sex-specific cancer incidence rates for Oslo 1988-1992. The number of non-AIDS-defining cancers was six (clinical CDC criteria) or eight (US AIDS definition), compared to expected numbers of 0.54 and 1.0, respectively. At autopsy, four of eight cases showed extensive tumor dissemination with involvement of the heart. These observations suggest that (at least some) non-AIDS-defining cancers occur at increased rates and show aggressive growth pattern in AIDS.

Nephrotic syndrome in a mother and her infant: relationship with cytomegalovirus infection.

This case report describes infantile nephrotic syndrome (NS) in a baby girl with a clinically severe cytomegalovirus (CMV) infection. Culture of the baby's urine was positive for CMV and IgM anti-CMV antibodies were detected. After an unsuccessful course of corticosteroids, gancyclovir treatment was started and a remission of cutaneous, pulmonary, and renal symptoms was achieved. As the mother also developed NS at the end of pregnancy, a common etiology could be postulated, although there were no signs of recent CMV infection in the mother, only anti-CMV IgG. The relationship between CMV infection and glomerular disease is still unclear; NS may represent another manifestation of CMV disease.

Immunotactoid-like glomerulopathy with massive fibrillary deposits in liver and bone marrow in monoclonal gammopathy.

At autopsy, massive nonamyloid fibrillar deposits, immunoreactive to IgG and kappa light chain, were found in glomeruli, liver, and bone marrow of a 72-year-old woman. The patient suffered from severe nephrotic syndrome, hepatomegaly and cholestasis, normochromic anemia, and IgG kappa monoclonal gammopathy. Fibrillary glomerulopathies, most often denoted as fibrillary glomerulonephritis or immunotactoid glomerulopathy, are generally considered to have deposits restricted to the glomeruli. However, this study indicates that fibrillary deposits may be a systemic manifestation of fibrillary glomerulonephritis or immunotactoid glomerulopathy, at least when the patient is suffering from a monoclonal gammopathy.

Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients.

Five years of normoglycemia following pancreas transplantation (PT) does not ameliorate glomerular lesions in patients with their own kidneys and with long-term insulin-dependent diabetes (IDDM) (Lancet 342:1193, 1993). All these patients received cyclosporine (CsA) as part of their immunosuppression. Here we examined the relationship of CsA dose and blood levels to the presence and severity of CsA-associated renal lesions and changes in renal function in these PT patients. Renal biopsies were taken before (0) and two and five years after PT from 13 non-uremic IDDM patients and were compared with baseline and five year biopsies from 10 IDDM controls (C). CsA dose was reduced from 10 +/- 3 mg/kg/day in the first month to 5 +/- 2 in the fifth year post-PT. Creatinine clearance (CCr) decreased by 34% at one year post-PT and was stable thereafter, and did not change in C. The decline in CCr from 0 to one year was related to CsA blood levels and dose (P < 0.005) at one year. Cortical interstitial volume fraction [Vv(Int/Cortex)], the index of tubular atrophy, and % sclerotic glomeruli increased significantly from 0 to five years post-PT (P < 0.005, 0.01 and 0.001, respectively), but did not change in C. There was no significant change from 0 to two years post-PT in these lesions, while there was a clear progression from two to five years. Mean CsA dose and blood levels in the first year post-PT correlated with the increase (delta) in Vv(Int/Cortex) at five years (P < 0.05 for both).(ABSTRACT TRUNCATED AT 250 WORDS)

Glomerulopathy associated with predominant fibronectin deposits: a newly recognized hereditary disease.

A newly recognized type of familial glomerulopathy observed in patients of both sexes in six families is reported. Proteinuria, often within the nephrotic range, microscopic hematuria, hypertension and a slowly decreasing renal function over several years were common. No underlying systemic diseases were identified. Generally, light microscopy showed enlarged glomeruli with minimal hypercellularity and with extensive deposits in the mesangium and subendothelial space. By electron microscopy, granular deposits with some admixture of fibrils were most common. In one family, the deposits were predominantly fibrillary. Immunoglobulins and complement factors were inconstant or lacking. A main finding was a strong immune reactivity to fibronectin, corresponding to the distribution of the deposits. In one patient, the deposits recurred in a renal transplant. There was no indication of systemic deposition. Abnormalities in the metabolism of circulating fibronectin may play a pathogenetic role in this disease of probably autosomal dominant inheritance.

Renal disease and patient survival in light chain deposition disease.

We evaluated retrospectively the presenting clinical features, response to treatment and clinical course of 19 patients with LCDD, 11 of whom had multiple myeloma. At presentation, renal insufficiency was present in 18 patients and proteinuria in 16. Renal biopsy revealed typical LCDD in 16 patients, while in the remaining three LCDD was associated with other abnormal tissue deposits. Extrarenal signs were observed in 12 patients (63%), with the liver, heart and peripheral nerves being the most frequently involved organs. After diagnosis, 18 patients underwent therapy: 2 received steroids alone and 16 were treated with steroids and cytotoxic drugs; 7 patients also underwent plasma exchange. At the end of the first month of treatment renal function improved in 5 patients, worsened in 5 and remained unchanged in 8. All but 3 of the patients continued treatment beyond the first month: 7 patients developed end-stage renal disease, 5 an improvement and 4 a worsening in renal function. No effect on proteinuria was observed. Extrarenal symptoms developed in 4 previously unaffected patients and in 3 others they extended to more organs. Sixteen patients died: 12 during the first year of the follow-up, and 4 at 21st, 34th, 37th and 82nd month of observation. Five patients died from neoplastic cachexia, 4 from hypokinetic cardiopathy, 3 from hemorrhagic complications, 2 from pneumonia and one from unknown cause. Mean patient survival after presentation was 18.1 +/- 20.7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Ciclosporin-associated arteriolopathy: the renin producing vascular smooth muscle cells are more sensitive to ciclosporin toxicity.

The pathogenesis of ciclosporin (Cs) induced renal vasoconstriction and CS-associated arteriolopathy (CAA) has not been fully explained. CAA affects the part of the afferent arteriole where renin is most abundant, and an effect by Cs on the renin producing smooth muscle cells leading to necrosis has been suggested. Forty transplant biopsies with CAA of different degrees were compared with 10 transplant biopsies from Cs treated patients without CAA, and with 10 "zero-hour" control biopsies (taken from the donor kidney at implantation). Immunoreactivity to renin by the ABC method was recorded in the arterioles. Compared to the control group there was a slight increase in the proportion of renin positive arterioles in the Cs treated group without CAA, but with increasing CAA there was a decrease in the proportion of renin positive arterioles. In the group of arterioles with CAA, we found that with increase in the severity of CAA, there was an increase in renin negative arterioles, indicating a loss of renin containing cells in these arterioles. This suggests that a large proportion of the necrotic cells in CAA has once been renin producing smooth muscle cells. Our findings support the possibility that Cs stimulates renin production, and that the renin producing cells are more sensitive to Cs toxicity.

Ocular pathology in light chain deposition disease.

Light-chain deposition disease (LCDD), a rare form of monoclonal gammopathy, is characterized by deposits of amorphous light-chain material, mainly in the kidneys but also in various other organs. Here we present the first report of a light-, electron microscopic and immunohistochemical study of the globes of a patient suffering from LCDD secondary to multiple myeloma. Massive deposits of kappa light chains similar to those typically present in the kidneys were found beneath the basement membrane of the ciliary pigment epithelium, on vessels of the ciliary body, within the collagenous zones of Bruch's membrane, and in the innermost part of the choroid. The choriocapillaris in the macular area was partly obstructed by these deposits, and an exudative retinal detachment was present. Whether this detachment was the consequence of disturbed circulation of the choriocapillaris remains speculative.