CT perfusion technique for assessment of early kidney allograft dysfunction: preliminary results.

OBJECTIVES: To assess the benefit of quantitative computed tomography (CT) perfusion for differentiating acute tubular necrosis (ATN) and acute rejection (AR) in kidney allografts. METHODS: Twenty-two patients with acute kidney allograft dysfunction caused by either AR (n = 6) or ATN (n = 16) were retrospectively included in the study. All patients initially underwent a multiphase CT angiography (CTA) protocol (12 phases, one phase every 3.5 s) covering the whole graft to exclude acute postoperative complications. Multiphase CT dataset and dedicated software were used to calculate renal blood flow. Renal biopsy or clinical course of disease served as the standard of reference. Mean effective radiation dose and mean amount of contrast media were calculated. RESULTS: Renal blood flow values were significantly lower (P = 0.001) in allografts undergoing AR (48.3 ± 21 ml/100 ml/min) compared with those with ATN (77.5 ± 21 ml/100 ml/min). No significant difference (P = 0.71) was observed regarding creatinine level with 5.65 ± 3.1 mg/dl in AR and 5.3 ± 1.9 mg/dl in ATN. The mean effective radiation dose of the CT perfusion protocol was 13.6 ± 5.2 mSv; the mean amount of contrast media applied was 34.5 ± 5.1 ml. All examinations were performed without complications. CONCLUSION: CT perfusion of kidney allografts may help to differentiate between ATN and rejection. KEY POINTS: • Quantitative CT perfusion of renal transplants is feasible. • CT perfusion could help to non-invasively differentiate AR from ATN. • CT perfusion might make some renal biopsies unnecessary.

Cutaneous vasculitis after renal transplantation: a case report.

BACKGROUND: Cutaneous vasculitis is a rare symptom after renal transplantation. With a broad spectrum of differential diagnosis, the new appearance of a skin rash in transplanted patients can be challenging. CASE REPORT: We present the case of a 69-year-old man with palpable purpura, skin ulcerations, and diffuse arthralgias. He had a history of cadaveric renal transplantation owing to biopsy-proven isolated immunoglobulin (Ig)A nephropathy and never suffered from any skin manifestation before. Skin biopsy confirmed Henoch-Schoenlein purpura (HSP), which developed under maintenance immunsuppressive therapy with tacrolimus and mycophenolate mofetil. Renal biopsy showed recurrent IgA nephropathy with positive mesangial and capillary IgA staining. DISCUSSION: This is the first case to describe a new manifestation of HSP following renal transplantation owing to isolated IgA nephropathy. Here, we summarize the differential diagnosis of cutaneous vasculitis following renal transplantation. Moreover we give a short review of the recurrence of IgA nephropathy and HSP after renal transplantation followed by possible strategies for prevention and therapy of recurrent disease.

[Orellanus syndrome: a rare cause of acute renal failure]. / Orellanus-Syndrom--seltene Ursache eines akuten Nierenversagens.

HISTORY AND CLINICAL FINDINGS: A 26-year-old woman with no contributory medical history became anuric after several days of nausea and vomiting. She was admitted to our hospital with suspected acute renal failure. INVESTIGATIONS: Laboratory tests revealed greatly elevated BUN and creatinine. There was no evidence of postrenal obstruction, infection or systemic disease. Kidney biopsy showed interstitial nephritis. DIAGNOSIS, THERAPY AND CLINICAL COURSE: Further questioning revealed poisoning with a nephrotoxic mushroom of the genus Cortinarius, which the patient had eaten together with her husband nine days before admission. The patient's husband developed anuric renal failure, too, and was admitted to our hospital. Hemodialysis was instituted on day 1. More than one year later, both patients remain on chronic dialysis. CONCLUSIONS: Intoxication with mushrooms of the genus Cortinarius should be considered in the differential diagnosis of otherwise unexplained acute renal failure, especially in autumn and late summer. These mushrooms can cause an interstitial nephritis. Once dialysis has to be instituted the prognosis is rather poor: 50 % of these patients develop chronic renal failure. So far there is no causative therapy. In case of chronic renal failure, kidney transplantation is possible.

Interstitial nephritis and high titers of PR3-ANCA: an unusual manifestation of ANCA-associated disease.

We present the case of a 75-year-old female with weight loss, anemia, systemic signs of inflammation, mild renal insufficiency, microscopic hematuria, mixed glomerular and tubular proteinuria, and high titers of PR3-ANCA. Renal biopsy demonstrated interstitial nephritis with some sclerosed but otherwise normal glomeruli. Extensive work-up showed no signs of granulomatous inflammation or other vasculitic organ involvement. We presumed this to be a rare renal manifestation of ANCA-associated disease with the presence of sclerosed glomeruli suggesting a previous history of glomerular involvement. In view of the absence of active vasculitic or granulomatous disease, treatment was limited to low-dose corticosteroids with good response.

[Persistent polyclonal B-cell lymphocytosis]. / Persistierende polyklonale B-Zell-Lymphozytose.

HISTORY AND CLINICAL FINDINGS: A 54-year-old woman was referred for ambulant checkup after an episode of acute renal failure due to severe gastroenteritis and recurrent arthralgias. Physical examination was unremarkable except for the presence of palpable small cervical lymph nodes. INVESTIGATIONS: Serum IgM levels showed a polyclonal increase. All the other routinely examined parameters were within normal limits. Microscopical blood smear examination revealed binucleated lymphocytes. Immunophenotyping of peripheral blood showed a polyclonal B-cell lymphocytosis despite normal numbers of leukocytes and lymphocytes. PCR analysis identified cells with a t(14;18) translocation (bcl-2/IgH rearrangement). DIAGNOSIS: A routine medical checkup disclosed the diagnosis of persistent polyclonal B-cell lymphocytosis. This rare benign lymphoproliferative disorder is characterized by binucleated lymphocytes, polyclonal expansion of B-cells, and a polyclonal increase in serum IgM. The diagnosis was established despite the lack of leukocytosis or lymphocytosis in the peripheral blood. CONCLUSIONS: Because of its benign and indolent course without the need for chemotherapy, it is important to discriminate the disorder of persistent polyclonal B-cell lymphocytosis from other malignant lymphoproliferative diseases.

Association of chronic lymphocytic leukemia with specific alleles of the HLA-DR4:DR53:DQ8 haplotype in German patients.

The etiology of chronic lymphocytic leukemia (CLL) remains unknown, though a genetic susceptibility has been suggested. Results of complete DNA typing of HLA alleles in CLL patients are lacking. We compared HLA class I and class II frequencies in 101 German CLL patients and 157 healthy German controls as determined by PCR-SSP/SSO DNA analysis and serologic typing. The most striking difference was the increased frequency of HLA-DRB4*0103 [relative risk (RR) = 2.74, p < 0.0025] among patients. The presence of alleles HLA-DRB1*0401, HLA-DQB1*0302 and HLA-DPB1*0301 as well as of homozygosity for HLA-DQB1 was also associated with a higher risk for CLL, though none of these differences remained significant after correction for multiple comparisons. No association was found for any HLA class I allele. Haplotype analysis revealed a CLL-specific linkage disequilibrium for HLA-DRB1*0401:DRB4*0103 and HLA-DRB4*0103:DQB1*0302. Our results suggest that CLL could be associated with distinct class II alleles of the Caucasian haplotype HLA-DR4:DR53:DQ8, which has also been related to a susceptibility for several auto-immune diseases. The positive, though weak, association of CLL with HLA-DPB1*0301 might represent an independent susceptibility factor since no linkage disequilibrium existed with any of the other CLL-associated alleles. None of the previously reported associations with HLA class I antigens was confirmed. Our results suggest that factors within or close to the human MHC class II region confer susceptibility to CLL.

Prevalence and spectrum of rheumatic diseases associated with proteinase 3-antineutrophil cytoplasmic antibodies (ANCA) and myeloperoxidase-ANCA.

OBJECTIVES: To evaluate the prevalence and association of antineutrophil cytoplasmic antibodies (ANCA) and their subtypes [proteinase 3 (PR3)-ANCA, myeloperoxidase (MPO)-ANCA] with distinct clinical features in various clinicopathological syndromes. METHODS: All consecutive ANCA-positive patients seen at the combined unit for rheumatology for Bad Bramstedt and the University of Lübeck between 1989 and 1999 were analysed. ANCA were detected by an immunofluorescence technique and ANCA subspecificities were determined by ELISA. Clinical features at presentation and diagnoses were recorded according to standardized procedures. RESULTS: Among 4620 patients tested, 333 were cytoplasmic ANCA-positive and 291 were perinuclear ANCA-positive. cANCA/PR3-ANCA were strongly associated with Wegener's granulomatosis (WG), whereas pANCA/MPO-ANCA were associated with a diverse disease spectrum. Further investigation of PR3-ANCA-positive (n=80) and MPO-ANCA-positive patients (n=40) revealed a greater extent of disease [disease extent index (DEI); median 8 vs 5, P<0.01] and more frequent involvement of the upper/lower respiratory tract and the eyes in PR3-ANCA-positive than in MPO-ANCA-positive patients. Fewer than 5% of WG patients were MPO-ANCA-positive. Compared with matched PR3-ANCA-positive WG patients, the MPO-ANCA-positive WG patients had a lower DEI (median 5 vs 8) and had a lower frequency of peripheral neuropathy. CONCLUSIONS: ANCA testing is useful due to its high sensitivity and specificity, especially for cANCA/PR3-ANCA in WG. We found a divergence in the disease spectrum between PR3- and MPO-ANCA-positive patients, characterized by higher DEI and extrarenal manifestations in the PR3-ANCA group. MPO-ANCA was rarely found in WG and was associated with less organ involvement.

Localized Wegener's granulomatosis: predominance of CD26 and IFN-gamma expression.

The immune response in Wegener's granulomatosis (WG) has been characterized as a predominant, potentially pathogenic Th1-like reaction by blood T cells and T-cell clones from diseased tissues. To elucidate further the immunopathogenic mechanisms, this study analysed the phenotypes of inflammatory infiltrates in frozen nasal biopsies with involvement of the upper respiratory tract only (localized or 'initial phase' WG) and with multi-organ involvement, including systemic vasculitis (generalized WG). The expression and production of Th1 and Th2 cytokines were examined in tissue specimens and peripheral blood mononuclear cells (PBMCs) of localized and generalized WG. The number of CD3+ T cells in inflammatory infiltrates ranged from 50 to 70%, together with approximately 30% CD14+ monocytes/macrophages. An average of 40% of T cells expressed CD26 in nasal biopsies of localized WG, compared with about 16% in specimens of generalized WG. In parallel, a higher number of interferon-gamma (IFN-gamma)-positive cells were detected in nasal tissue of localized than in generalized WG. PBMCs from localized WG similarly exhibited higher spontaneous IFN-gamma production in contrast to generalized WG (207 vs. 3 pg/ml, p<0.05). Interleukin-4 (IL-4) mRNA was found in higher amounts in generalized than in localized WG. IL-4 production was negligible in both disease and controls. In addition, both IL-10 mRNA and IL-10 protein levels of activated PBMCs from localized WG were elevated when compared with generalized disease (574 vs. 154 pg/ml, p<0.05) or healthy controls (574 vs. 246 pg/ml, p<0.05). It is conluded that in nasal tissues, mainly CD4+/CD26+ T cells as well as IFN-gamma-positive cells may support a polarized Th1-like immune response. Furthermore, the data suggest that this in situ immune response is already initiated and established in localized WG, accompanied by increased peripheral IFN-gamma and IL-10 production.

Circulating cytokines and soluble CD23, CD26 and CD30 in ANCA-associated vasculitides.

OBJECTIVE: To assess circulating immunoregulatory cytokines and soluble surface markers of T and B cell activation in the plasma of patients with Wegener's granulomatosis (WG), Churg-Strauss syndrome (CSS) and microscopic polyangiitis (MPA) during active and inactive disease, in order to establish their value in discriminating between disease entities and as markers of disease activity. METHODS: Plasma levels of IL-4, IL-5, IL-10, IL-12, IL-13, IFN-gamma and soluble CD23, CD26 and CD30 were determined by enzyme-linked immunosorbent assay in patients with WG (n = 21), CSS (n = 19) and MPA (n = 14) during active disease and remission. RESULTS: Concerning cytokines, no differences were observed for IFN-gamma, IL-4, IL-5 and IL-13. Plasma levels of IL-12 were decreased in all subgroups of patients. On the contrary, IL-10 levels were significantly elevated only in patients with CSS. Levels of sCD30 were significantly increased in patients with active generalized WG and CSS, but not in those with MPA and localized WG, correlating with the disease extent and activity. sCD26 levels were markedly decreased in patients with generalized WG, CSS and MPA and increased towards remission. sCD23 levels were slightly, but not significantly increased in CSS and generalized WG. CONCLUSION: Regarding the investigated immunoregulatory cytokines (Th1/Th2 type), only the measurement of plasma levels of IL-10 discriminated CSS from WG and MPA. The reported data could indicate a similar status of T cell activation in generalized WG and CSS, and possibly a shift in peripheral immunity towards a more humoral dominated immune response. The differences observed between patients with the localized and generalized forms of WG seem to reflect the clinically known biphasic course of this disease.