Search

Eine 43-jahrige Patientin mit seit 1 Jahr bestehenden rezidivierenden beidseitigen Uveitiden, die jeweils mit relativen hohen Glukokortikoiddosen systemisch behandelt werden mussten, wurde wegen einer neu aufgetretenen renalen Funktionseinschrankung und Proteinurie zur rheumatologisch-nephrologischen Differenzialdiagnostik in unsere Klinik eingewiesen. Die Nierenhistologie zeigte eine tubulointerstitielle Nephritis, Hinweise auf eine Glomerulonephritis fanden sich nicht. Da sich weder anamnestisch noch bei weiterfuhrenden Untersuchungen Hinweise auf eine entzundlich rheumatische Grunderkrankung ergaben – HLA B27 und ANCA (antizytoplasmatische Antikorper) waren negativ –, wurde in Ubereinstimmung mit dem pathologischen Befund der Nierenbiopsie die Diagnose Tubulointerstitielle-Nephritis-mit-Uveitis (TINU)-Syndrom gestellt. Eine medikamentos toxische interstitielle Nephritis erschien weniger wahrscheinlich [12]. Da die Erkrankung unter der bisherigen Therapie mit Prednisolon und Ciclosporin nicht ausreichend kontrolliert war und die Patientin bereits einen cushingoiden Habitus entwickelt hatte, stellten wir die Indikation fur eine kombinierte Therapie mit dem TNF-α-Blocker Adalimumab und Methotrexat. Hierunter ist die Patientin jetzt seit 6 Monaten bezuglich der Uveitis rezidivfrei. Die Glukokortikoidtherapie konnte erstmals seit 2 Jahren verlassen werden. Die Nierenfunktion hat sich bemerkenswerterweise komplett erholt. Dieser Verlauf legt die Vermutung nahe, dass TNF an der Pathogenese des TINU-Syndroms wesentlich beteiligt ist. Daruber hinaus ist dieser Fall das erste publizierte Beispiel fur eine erfolgreiche Anti-TNF-Therapie bei dieser seltenen Erkrankung.

Hintergrund Das Cholesterinembolie-Syndrom ist eine unterschatzte Komplikation nach Katheterinterventionen an arteriellen Gefasen. 8–10 Wochen nach dem Eingriff zeigen die Patienten akutes Nierenversagen, Zyanose der Fuse und weitere dermatologische Befunde, Diarrhoen und anderes.

Anamnese und klinischer Befund: Mit 2017 gemeldeten Fallen fand 2010 die bisher groste Hantavirus-Epidemie in Deutschland statt. Wir berichten uber zwei besondere Falle, die die Bandbreite der klinischen Manifestation der Hantavirus-Erkrankung und die Fallstricke der Diagnostik verdeutlichen sollen. Im ersten Fall eines schwer erkrankten dialysepflichtigen 44-jahrigen Patienten mit einer ursprunglich grippalen Symptomatik und rasch eintretender Oligurie lenkte eine auswarts negativ bestimmte Hantavirus-Serologie den Fokus auf eine rapid-progressive Glomerulonephritis, im Fall 2 stand bei einem 22-jahrigen mannlichen Patienten eine schwere neurologische Symptomatik mit konvulsiven Episoden im Vordergrund. Untersuchung, Therapie und Verlauf: Die histologische Begutachtung der Nierenbiopsie in Fall 1 ergab das klassische Bild eines tubulointerstitiellen Schadens der Nierenrinde und des auseren Marks wie bei Hantavirus-Infektionen. Eine erneute virologische Untersuchung konnte dann auch im EDTA-Plasma Puumalavirus-RNA als Akutmarker nachweisen. Nach mehreren Hamodialysen und einem Steroidbolus kam es zu einer langsamen klinischen Besserung. Im Fall 2 fuhrte die zunachst schwere neurologische Symptomatik zu einer umfassenden Diagnostik einschlieslich Liquorpunktion und MRT, bevor im weiteren Verlauf durch den Nachweis spezifischer Antikorper und Puumalavirus-RNA eine Nephropathia epidemica als Erkrankung diagnostiziert wurde. Der Patient erholte sich nach 10 Tagen. Folgerung: Die Nephropathia epidemica kann in seltenen Fallen aufgrund der Symptomvariabilitat und auch begleitender extrarenaler Manifestationen differenzialdiagnostische Probleme bereiten. Aufgrund der Analogie zu anderen aggressiven renalen Erkrankungen ist eine schnelle Diagnosestellung wichtig.

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. Binding of circulating autoantibodies to the glomerular filtration barrier leads to the development of this autoimmune disease. The clinical symptoms range from small proteinuria to severe nephrotic syndrome with enormous oedema, not controllable hyperlipidaemia and increased disposition for infection. One third of patients reach complete or partial remission of proteinuria under symptomatic treatment, which includes ACE-inhibitors and AT-I-blockers, loop diuretics and statins. Untreated the disease leads to loss of renal function over 5-10 years in 20-30% of patients. A risk score based on proteinuria and renal function is used to guide the decision when to start with an immunosuppressive therapy. A better adapted diagnostic and therapy of membranous nephropathy may be possible through measurement of circulating autoantibodies directed against a podocytic phospholipase-A(2) receptor.

Die hantavirusinduzierte Nephropathia epidemica (NE) gilt als prognostisch gunstige Variante des hamorrhagischen Fiebers mit renalem Syndrom. In den ersten 9 Monaten des Jahres 2010 wurden in Deutschland schon mehr als 1700 serologisch gesicherte Erkrankungsfalle gemeldet. Die typische Symptomatik (akuter Beginn mit hohem Fieber, Myalgien, akutes Nierenversagen, Thrombozytopenie, Hamaturie, grose Proteinurie) kann v. a. bei schweren Verlaufsformen eine Nierenbiopsie zur differenzialdiagnostischen Abklarung erfordern. Nach kombinierter lichtmikroskopischer, immunhistochemischer und elektronenmikroskopischer Aufarbeitung ergibt sich in der Regel ein fur die NE charakteristisches Befundmuster (im auseren Mark: herdformige interstitielle Nephritis mit multifokalen Hamorrhagien, Endotheldefekte und Thrombozytenaggregate in peritubularen Kapillaren; in der Rinde: diffuser reversibler proximaler Tubulusschaden und normale Glomeruli), das eine zuverlassige differenzialdiagnostische Abgrenzung gegenuber interstitiellen Nephritiden anderer Ursache, verschiedenen Glomerulonephritisformen, leukozytoklastischen Vaskulitiden und thrombotischen Mikroangiopathien erlaubt.

Die membranoproliferative Glomerulonephritis Typ I tritt selten als primare, idiopathische Erkrankung auf, viel haufiger infolge sehr unterschiedlicher Grunderkrankungen. Zu diesen zahlen Autoimmunerkrankungen, wie systemischer Lupus erythematodes und Kryogloblulinamie, chronische Infektionen, wie Hepatitis und Endokarditis, und maligne Erkrankungen. Eine paraneoplastische Glomerulonephritis wird insbesondere bei chronisch lymphozytischer Leukamie beobachtet. Wir zeigen hier am Beispiel einer sekundaren membranoproliferativen Glomerulonephritis Typ I bei Non-Hodgkin-Lymphom vom B-Zell-Typ, wie die Therapie der Grunderkrankung – in diesem Fall ein einziger Zyklus Rituximab/Bendamustin – zur weitestgehenden Ausheilung der membranoproliferativen Glomerulonephritis fuhrte.

Als Multisystemerkrankungen konnen systemische Amyloidosen durch renale Symptome klinisch apparent werden; u. a. sind sie wichtige Differenzialdiagnosen des nephrotischen Syndroms. Sie konnen zu irreversiblen Nierenschadigungen fuhren. Ziel der Amyloidosebehandlung ist die Stilllegung der Quelle der Amyloidvorstufen durch Beherrschung der Grunderkrankung. Ansatze mit Substanzen, welche die Ablagerung von Amyloid hemmen bzw. dessen Auflosung beschleunigen, befinden sich noch in der Erprobung. Bei den deutlich selteneren hereditaren Amyloidosen, die auf fibrillogenen Mutationen verschiedener fur Proteine kodierender Gene beruhen, und masgeblich hepatischer Synthese des Vorlauferproteins ist eine Lebertransplantation eine therapeutische Option.

Glomerular epithelial cell (podocyte) injury is characterized by foot process retraction, slit diaphragm reorganization, and degradation of podocyte-specific proteins. However, the mechanisms underlying podocyte injury are largely unknown. The ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a key modulator of ubiquitin modification in neurons. Like neurons, UCH-L1 expression was associated with an undifferentiated status in cultured human podocytes, whereas differentiation and arborization decreased UCH-L1 and monoUb expression. Inhibition of UCH-L1 induced time and concentration-dependent process formation with α-actinin-4 distribution to the cell membrane and processes. An immunohistochemical approach was used to evaluate whether UCH-L1 expression was associated with podocyte injury in 15 different human glomerular diseases. Whereas normal kidneys expressed no UCH-L1 and little ubiquitin, a subset of human glomerulopathies associated with podocyte foot process effacement (membranous nephropathy, SLE class V, FSGS) de novo expressed UCH-L1 in podocyte cell bodies, nuclei, and processes. Interestingly, UCH-L1 expression correlated with podocyte ubiquitin content and internalization of the podocyte-specific proteins nephrin and α-actinin-4. In contrast, minimal change glomerulonephritis, a reversible disease, demonstrated minimal UCH-L1 and ubiquitin expression with intact α-actinin-4 but internalized nephrin. Glomerular kidney diseases typically not associated with foot process effacement (SLE class IV, ANCA+ necrotizing GN, amyloidosis, IgA nephritis) expressed intermediate to no UCH-L1 and ubiquitin. These studies show a role for UCH-L1 and ubiquitin modification in podocyte differentiation and injury. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Wir berichten uber einen 42-jahrigen Patienten mit einem Nebennierenrindenkarzinom, der aufgrund eines bilateralen Visusverlusts und einer hypertensiven Entgleisung aufgenommen wurde. Zusatzlich bestand eine hamolytische Anamie, eine Thrombozytopenie und eine Erhohung der Retentionswerte. Demzufolge wurde die Diagnose einer Gemcitabin-assoziierten thrombotischen Mikrangiopathie gestellt. Unter Therapie mit Prednisolon und antihypertensiver Medikation stabilisierte sich der Patient und erlangte die volle Sehkraft zuruck. Eine Plasmapherese wurde nicht notwendig. Die thrombotische Mikroangiopathie sollte als seltene Komplikation einer Gemcitabintherapie stets bedacht werden.

Renale Symptome (grose Proteinurie, nephrotisches Syndrom, beginnende Niereninsuffizienz) und ihre bioptische Abklarung fuhren am haufigsten zur Ersterkennung einer systemischen Amyloidose. Fur die individuelle Therapieplanung ist die immunhistochemische Amyloiddifferenzierung unerlasslich. Als etablierte Behandlungsstrategie gilt die Ausschaltung der jeweiligen Vorlauferproteine, entweder durch eine gegen Plasmazellen gerichtete Chemotherapie mit oder ohne Stammzelltransplantation bei AL- oder durch eine gezielte antiphlogistische Behandlung bei AA-Amyloidosen. Dadurch erzielte Therapieerfolge, die Absenkung der Proteinurie und die Verbesserung der exkretorischen Funktion, sind wahrscheinlich nicht an eine Herauslosung des im Gewebe abgelagerten Amyloids gebunden.

History and clinical findings An 82-year-old woman with hypertension for 20 years developed a nephrotic syndrome with severe oedema followed by acute oliguric renal failure after a bout of bronchitis and a gastrointestinal infection. She also complained of xerostomia and dry eyes of recent onset. Investigations Biochemical tests showed a serum creatinine level of 6.1 mg/dl, a 1:5120 antinuclear antibody (ANA) titre, and positive values for Ro(SS-A) and La(SS-B) antibodies. HLA-DR typing demonstrated HLA-DR3 (HLA-DRB1*0301) and DR13 (HLA-DRB1*13) antigens. Renal biopsy revealed minimal glomerular lesions with focal and segmental glomerulo-sclerosis as well as (hypertension-induced) benign nephrosclerosis and focal tubular atrophy with interstitial fibrosis. Treatment and course After two hemofiltrations and concomitant administration of 100 mg prednisone renal function quickly improved and the proteinuria fell to 1 g/dl. At the same time the xerostomia improved. The nephrotic syndrome recurred 7 months later after the prednisone dose had been reduced to 10 mg/d, but after the dose had been raised to 50 mg/d and cyclosporin A (150 mg/d) had been added a lasting remission occurred and renal function became stable though impaired. Conclusion The relatively rare association of glomerular disease (here focal segmental glomerulosclerosis) with Sjogren's syndrome can, as in this case, be triggered by a viral infection. A genetic predisposition for Sjogren's syndrome is suggested by the demonstration of HLA-DR3 alleles. Administration of steroids is indicated for the treatment of the nephrotic syndrome and, in case of recurrence, can be combined with cyclosporin A. Both drugs also influence the symptoms of Sjogren's syndrome.

Anamnese und klinischer Befund: Bei einem 52jahrigen Mann waren seit 2 Jahren wiederholt eine Purpura, Arthralgien und Fieber aufgetreten. Eine monoklonale Gammopathie vom IgG-Lambda-Typ sowie eine Vaskulitis waren bereits bekannt, als der Patient an einem neuen Schub mit akutem Nierenversagen und nekrotisierenden Ulcera an den unteren Extremitaten erkrankte. Untersuchungen: Pathologisch verandert waren Blutsenkungsreaktion (122 mm), Hamoglobinspiegel (9.1 g/dl), Thrombozytenzahl (562 000/µl), Leukozytenzahl (32 000/µl), Kreatininspiegel (4.1 mg/dl), Harnstoff-Stickstoff-Spiegel (78 mg/dl) und die Aktivitaten der Leberenzyme, ferner bestanden eine Proteinurie (4,5 g/d) und ein nephritisches Sediment. Das monoklonale Immunglobulin wurde als IgG3 subtypisiert, die weiterfuhrenden Untersuchungen ergaben eine Kryoglobulinamie. Der Gesamtkomplementspiegel (CH 50) war nicht mesbar. Das Knochenmarkaspirat ergab eine Infiltration durch ein Plasmozytom, das Nierenbiopsat eine nekrotisierende Arteriitis sowie granulare subendotheliale Ablagerungen von IgG3 und Komplement. Therapie und Verlauf: Nach drei Plasmaseparationen und Einleitung eines ersten Vineristin-Doxorubicin-Dexamethason-Zyklus uber 4 Tage sank der Kreatininspiegel in den Normbereich, die Nekrosen heilten langsam ab. Seit inzwischen 24 Monaten besteht klinisch keine Krankheitsaktivitat, obwohl weiterhin Kryoglobulin nachweisbar ist. History and clinical findings: For 2 years a 52-year-old man had repeated bouts of purpura, arthralgia and fever. He was known to have abnormal monoclonal gammaglobulins, type IgG-lambda and vasculitis when he had another bout with acute renal failure and necrotizing ulcers in the legs. Tests: Several laboratory tests were abnormal: erythrocyte sedimentation rate (122 mm), haemoglobin level (9.1 g/dl), white cell count (32 000/µl), platelet count (562 000/µl), creatinine level (4.1 mg/dl) and liver enzyme activities. He also had proteinuria (4.5 g daily) and nephritic urinary sediments. The immunoglobulin was subtype IgG3, and a cryoglobulinaemia was also present. Total complement level (CH 50) was not measurable. Bone marrow aspirate revealed plasmocytoma infiltration, and renal biopsy demonstrated necrotizing arteritis, as well as granular subendothelial deposits of IgG and complement. Treatment and course: After three plasma separations and initiation of the first treatment cycle with a four-day infusion of vincristine, doxorubicin and dexamethasone the creatinine concentration fell to within the normal range and the necroses healed slowly. No cryoglobulin activity has been demonstrable over the past 24 months.

Die diabetische Nephropathie ist die haufigste Ursache der terminalen Niereninsuffizienz. Im Zentrum der diabetischen Nephropathie steht die Glomerulosklerose. Sie bildet das morphologische Korrelat der Proteinurie. Pathogenetisch sind gesteigerte glomerulare Matrixbildung und Hyperglykamie eng miteinander verknupft. Qualitativ gleichartige diabetische und hypertensive praglomerulare Gefaswandschaden verschlimmern die Glomerulosklerose. Unabhangig von seiner Blutdruckwirkung ist Angiotensin II ein weiterer ursachlicher Glomerulosklerosefaktor. Die Normalisierung von Blutzucker und Blutdruck, die Blockade von Angiotensin II und die Erfassung zusatzlicher Nierenerkrankungen bedeuten eine wissenschaftlich gut begrundete Strategie fur die Bekampfung der diabetischen Nephropathie.

Eine Sarkoidose der Niere kann isoliert oder im Rahmen einer Systemerkrankung auftreten. Als diagnostisches Leitsymptom dient eine Nierenfunktionsverschlechterung, deren Ursache interstitielle Nephritiden, Glomerulonephritiden oder eine Kalziumnephropathie sein konnen. Eine Nierenbiopsie ist als wertvolles, differentialdiagnostisches Kriterium fruhzeitig indiziert. Storungen des Kalziumstoffwechsels konnen ebenfalls diagnostisch wegweisend sein. Unter Therapie mit Steroiden kommt es in den meisten Fallen einer Sarkoidose der Niere zu einer guten Restitution der Nierenfunktion. Wesentlich ist, bei einer Niereninsuffizienz unklarer Atiologie eine Sarkoidose in die differentialdiagnostischen Uberlegungen einzubeziehen und fruhzeitig mit einer adaquaten Therapie zu beginnen, um Spatschaden zu verhindern.

Prostaglandin E1 inhibits collagen expression in anti-thymocyte antibody-induced glomerulonephritis: Possible role of TGFβ. To test whether or not prostaglandins mediate extracellular matrix formation in immune-mediated glomerular disease, rats with anti-thymocyte antibody-induced glomerulonephritis were treated with prostaglandin E1 (PGE 1 ) (250 μ g/twice daily/s.c.). Glomerular expression of collagen types III and IV was assessed by Northern blotting, immunohistology and Western blotting. Proliferation of glomerular cells was evaluated by staining for the proliferating cell nuclear antigen (PCNA) and consecutive cell counting. At day five after induction of the disease, glomerular mRNA levels of collagen types III and IV were three- to fivefold higher compared with non-nephritic controls. Similarly glomerular deposition of these collagens was markedly increased when assessed by immunohistology. The treatment of nephritic rats with PGE 1 reduced the increased glomerular mRNA levels as well as the protein concentration and the deposition of extracellular collagens. The number of PCNA positive cells which was significantly higher in nephritic rats when compared with control animals (24 hr, nephritis 2.53 ± 0.33 and Control 0.26 ± 0.06, P = 0.011; 5 days, nephritis 5.10 ± 1.13 and Control 0.75 ± 0.08, cells per glomerular cross section, P = 0.03) was reduced by PGE 1 (24 hr, nephritis + PGE 1 0.44 ± 0.30, P=0.0001; 5 days, nephritis + PGE 1 1.91 ± 1.84 cells per glomerular cross section, P = 0.001). Prostaglandin E 1 also ameliorated the glomerular infiltration of monocytes at 24 hours (nephritis 4.36 ± 2.82, nephritis + PGE 1 2.20 ± 1.82, cells per glomerular cross section) and five days (nephritis 1.51 ± 0.58, nephritis + PGE 1 1.12 ± 0.61, cells per glomerular cross section). To further characterize possible mechanisms by which PGE 1 reduces extracellular matrix deposition, the glomerular expression of transforming growth factor (TGF- β ), and interleukin 1 β (IL-1 β ) was assessed by Northern blotting. Nephritic glomeruli showed increased mRNA levels of TGF- β at day 5 and IL-1 β at 24 hours when compared with control kidneys. Treatment of the animals with PGE 1 inhibited the mRNA expression of TGF- β and IL-1 β . These data demonstrate that PGE 1 reduces the glomerular expression of extracellular matrix proteins in anti-thymocyte antibody-induced glomerulonephritis, suggesting a beneficial role of prostaglandins in this proliferative glomerular immune injury. The effects of PGE 1 might be mediated by inhibition of TGF- β and IL-1 β production.

Renal biopsy is generally indicated in cases of systemic lupus erythematosus with clinical signs of renal involvement. Classification should be made according to the modified WHO criteria, classes I to VI on light microscopic, immunohistological, and electron microscopic grounds. The result should include activity and chronicity criteria. Without appropriate treatment, prognosis is especially poor in patients with WHO class III or IV (sometimes also V) lupus nephritis. Repeat renal biopsies can monitor the degree of chronic tubular and glomerular damage and thus help in deciding whether to continue ongoing aggressive therapy. Bei systemischem Lupus erythematodes mit klinischen Zeichen einer Nierenbeteiligung sollte in der Regel mindestens eine aussagekraftige Nierenbiopsie einschlieslich mehrerer Glomeruli und Tubulus-Anteilen erfolgen. Auf der Grundlage lichtmikroskopischer, immunhistologischer und elektronenmikroskopischer Kriterien sollte die Klassifikation nach den modifizierten WHO-Kriterien in die Klasse I bis VI erfolgen. Zusatzlich sind Aussagen uber den Aktivitatsgrad und den Chronizitatsgrad sinnvoll. Speziell bei Vorliegen der WHO-Kriterien III oder IV (teilweise auch V) mit hoher Aktivitat und geringer Chronizitat kann ohne adaquate Therapie von einer schlechten Prognose ausgegangen werden. Verlaufsbiopsien konnen anhand des Ausmases der dann haufig vorliegenden tubularen Schaden und der Chronizitat pathologischer Veranderungen zur Entscheidung beitragen, ob eine aggressive Behandlung weitergefuhrt werden sollte.

CD66a, also called biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily. CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule of the rat. In the present study a monoclonal antibody specific for CD66a was used to locate CD66a in human tissues. CD66a is expressed in epithelia, in certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained along the bile canaliculi. A characteristic apical membranous staining was observed in enterocytes, superficial absorptive cells of the colon, in the epithelia of esophageal and Brunner's glands, bile ducts and gallbladder, pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and mammary ducts. Selective staining of endothelia was present in glomeruli and vasa recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes were positive. The expression of CD66a by human cells and tissues is well comparable with the expression reported for Cell-CAM, the rat counterpart of CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent human adhesion molecule.

The tubulo-interstitial nephritis and uveitis (TINU) syndrome, first described in 1975, is a rare disease most probably of autoimmune origin that is characterized by unilateral or bilateral uveitis and tubulointerstitial nephritis. Most patients are adolescents and it is sometimes associated with other autoimmune diseases, such as spondyloarthritis, rheumatoid arthritis and hyperthyroidosis. This article reports the case of a 43-year-old female patient who presented with refractory recurrent bilateral uveitis despite therapy with high doses of corticosteroids in combination with cyclosporin. When the patient was referred to this hospital for rheumatological examination after almost 1 year of therapy, mild renal insufficiency and proteinuria were found. The kidney biopsy revealed interstitial nephritis, partly crescent-shaped and partly chronic. A diagnosis of TINU syndrome was made and treatment with adalimumab in combination with methotrexate was started. The favorable clinical outcome indicated that tumor necrosis factor (TNF) alpha may play an important role in the pathogenesis of TINU syndrome.

With 2017 notified cases the largest hantavirus epidemic in Germany has occurred in 2010. We report on two interesting cases illustrating the wide range of the individual clinical course and the diagnostic problems in hantavirus disease. The first patient was a seriously ill 44-year-old man who needed dialysis after an onset of flu-like symptoms with oliguria. An initially negative result of a hantavirus serology focused attention on rapidly progressive glomerulonephritis. The second patient, a 22-year-old man, presented with severe neurological symptoms with seizures.Pathological examination of the renal-biopsy specimen in Case 1 reportedly showed the typical pattern of tubulointerstitial damage in the renal cortex and the outer medulla as in hantavirus infection. In a repeated analysis Puumala virus RNA as a marker of acute infection was found. After dialysis and administration of higher-dose systemic glucocorticoids the patient slowly recovered. In Case 2 the severe neurological symptoms caused a complete neurological diagnostic with lumbar puncture and MRI before the detection of specific antibodies and Puumala virus RNA showed that nephropathia epidemica was the disease. The patient recovered after 10 days.Because of the variability of symptoms and the extrarenal manifestations of the disease the nephropathia epidemica can occasionally cause problems of differential diagnosis. A rapid diagnosis is important because of the urgent differentiation of other renal diseases with bad prognosis.

Visceral leishmaniasis (kala-azar) affecting HIV-infected patient is being reported in increasing frequency. A 40-year-old German bisexual patient with full-blown AIDS is described who presented with Kaposi's sarcoma, epigastric pain, diarrhea, and weight loss but without fever. Leishmania amastigotes were initially found in biopsies from stomach, duodenum, and a cutaneous Kaposi's sarcoma lesion but were later also recovered from bone marrow and lymph node. The patient received three courses of a combination of pentavalent antimony and interferon-gamma. In addition to the common side effects such as fever, thrombocytopenia, and elevated amylase and lipase, a vivid progression of the Kaposi's sarcoma was noted. Tumor progression was temporally closely associated with treatment with interferon-gamma. Because this phenomenon has also been observed in other patients, we advise caution when using interferon-gamma in patients with Kaposi's sarcoma.

Membranous nephropathy is the most common cause of nephrotic syndrome in adults. Binding of circulating autoantibodies to the glomerular filtration barrier leads to the development of this autoimmune disease. The clinical symptoms range from small proteinuria to severe nephrotic syndrome with enormous oedema, not controllable hyperlipidaemia and increased disposition for infection. One third of patients reach complete or partial remission of proteinuria under symptomatic treatment, which includes ACE-inhibitors and AT-I-blockers, loop diuretics and statins. Untreated the disease leads to loss of renal function over 5-10 years in 20-30% of patients. A risk score based on proteinuria and renal function is used to guide the decision when to start with an immunosuppressive therapy. A better adapted diagnostic and therapy of membranous nephropathy may be possible through measurement of circulating autoantibodies directed against a podocytic phospholipase-A(2) receptor.

Among a total of 2147 patients admitted to our hospital for acute myocardial infarction between 1978 and 1987, three young patients aged 24, 29, and 39 years had previously been treated for Hodgkin's disease. Staging laparotomy, including splenectomy, had been performed in all three patients. Two patients had both mediastinal irradiation (21 and 27 months before infarction) and chemotherapy. In the first patient, postmortem histologic examination of the coronary arteries revealed fibrotic changes, which were probably induced by radiotherapy. In our second patient, myocardial infarction developed 5 days after vinblastine treatment; early angiography showed thrombotic occlusion of the proximal right coronary artery, which was recanalized using the diagnostic Sones catheter. Subsequent angiography revealed normal coronary arteries. This is, to our knowledge, the first case of documented coronary artery thrombosis after treatment with vinca-alkaloids. In our third patient, neither mediastinal irradiation nor chemotherapy had been performed prior to myocardial infarction. However, a marked increase in platelet counts following splenectomy was observed in this patient. The role of radiotherapy, chemotherapy, and splenectomy with consecutive thrombocytosis as a third possible pathogenic factor for subsequent development of myocardial infarction is discussed.

We report a case of a 42 year old male patient with a history of adrenocortical carcinoma, who was admitted with bilateral loss of sight and hypertension. Laboratory tests and further clinical evaluation showed hemolytic anemia, thrombocytopenia and acute renal failure. This was consistent with thrombotic microangiopathy / hemolytic uremic syndrome (HUS) due to gemcitabine therapy. The patient was successfully treated with prednisolon and antihypertensive drugs. Visus was completely restored, plasmapheresis was not needed. Clinicians should be aware of HUS as a rare complication of gemcitabine therapy.

Immune-mediated mesangial cell injury—Biosynthesis and function of prostanoids. We studied the formation of cyclo-oxygenase products in a rat model of mesangial cell injury, in order to determine a possible role of prostaglandin E2 (PGE2), prostaglandin I2 (determined as 6-keto-PGF1α and thromboxane A2 (TxA2) in immune-mediated glomerular disease. Selective immune-mediated mesangial cell injury was induced by i.v. administration of a rabbit anti-rat thymocyte antiserum (ATS). Intravenous ATS leads to immune deposits in the mesangium followed by mesangiolysis and the infiltration of polymorphonuclear granulocytes and monocytes. Glomerular TxB2 formation two hours (292 ± 27 pg/mg/min) and 48 hours (396 ± 69 pg/mg/min) following antibody was significantly (P < 0.05) higher compared to animals receiving non-antibody rabbit IgG (TxB2: 2hr 143 ± 13; 48hr 171 ± 32 pg/mg/min). Treatment with cobra venom factor (CVF) and the reduction of glomerular monocyte infiltration inhibited the increase of glomerular TxB2 formation significantly. Depletion of granulocytes with a rabbit anti-rat granulocyte serum had no effect on glomerular prostanoid formation following ATS. Glomerular PGE2 and 6-keto PGF1α production was not altered following ATS. Inulin clearance in rats with immune-mediated mesangial cell injury was significantly (P < 0.001) lower at two hours (456 ± 24 µl/min/100g body wt) and 48 hours (433 ± 54 µl/min/lOO g body wt) compared to their corresponding control animals which were treated with non-antibody IgG (2 hr: 914 ± 51; 48 hr: 694 ± 79 µl/min/100g body wt). Pretreatment of rats with indomethacin (Indo) or with the thromboxane synthetase inhibitor UK 38485 prevented the decrease in inulin clearance following ATS at two hours (Indo: 800 ± 67; UK 38485: 923 ± 115) and at 48 hours (Indo: 697 ± 60; UK 38485: 654 ± 99). The data demonstrate that selective, immune-mediated mesangial cell injury in rats is associated with increased glomerular TxB2 formation. Complement and monocyte/macrophage depletion reduces TxB2 production. The fall in inulin clearance following ATS is ameliorated when the rats receive indomethacin or the Tx synthetase inhibitor UK 38485. Thus, elevated TxB2 formation might mediate the reduction in GFR in this model of glomerular immune injury.

Hantaviruses belong to the so-called emerging pathogens that are transmitted to humans by infected rodents and their excreta. In Central Europe, hantavirus infections usually occur in a mild to moderate form of hemorrhagic fever with renal syndrome. In contrast to the mostly benign or even asymptomatic course of hantavirus infections in previously healthy individuals, the acute hantavirus infection in kidney transplant recipients represents an exceptional situation regarding diagnosis and therapy. We describe the case of a 44-year-old kidney transplant recipient with acute renal transplant failure associated with acute hantavirus infection.

We report on a 67-year-old female patient who was admitted to our intensive care unit with acute renal failure and severe hypoxemia. Transiently, the patient had to be treated with kidney replacement therapies and artificial ventilation. The actual illness started with general weakness, recurrent bloody diarrhea and intermittent dermatitis of the lower legs. Skin symptoms were initially observed 2 years before the actual clinical findings. The bloody diarrhea was attributed to an inflammatory stenosis of the sigma. The life-threatening clinical aggravation was due to diffuse alveolar hemorrhage and alveolitis. In the search for the cause of the systemic disease, both a monoclonal y-globulinemia, causing a cryoglobulinemia type II and an acute cytomegalovirus infection were diagnosed. Additionally, the course of the disease was complicated by a secondary antibody deficiency as well as an endocarditis of the aortic valve caused by Enterococcus faecium. A cryoglobulinemic vasculitis type II was histologically found in biopsy specimen of the kidney. Thus, the present case reports on a coincidence of a monoclonal gammopathy causing a cryoglobulinemia type II with extensive organ involvement and a florid CMV infection. We hypothesize that the CMV infection has triggered the cryoglobulinemia and its particular severe organ involvement.

A 40-year-old woman underwent ultrasound-guided renal biopsy after having received a kidney transplant 6 years ago. Her creatinine level was 4.5 mg/dl. The biopsy contained renal cortex with glomeruli (Figure 1a); a tangentially sectioned large artery, potentially an interlobar caliber vessel (Figure 1b); and urothelium from the renal pelvis (Figure 1c). Within minutes, massive macrohematuria and hemorrhagic shock occurred. To avoid loss of the transplant due to nephrectomy, digital subtraction angiography using gadolinium was immediately performed. This detected intragraft active bleeding that also involved the renal pelvis (Figure 2a, arrow). With the use of four endovascular microcoils, two small peripheral intrarenal arteries were embolized. Control arteriography confirmed the successful embolization, and hemorrhage ceased (Figure 2b, arrow). The patient's condition promptly stabilized. The patient was discharged with a functioning allograft.

We report on successful induction of remission in a patient with necrotizing crescentic glomerulonephritis associated with myeloperoxidase-antineutrophil-cytoplasm antibodies by primary use of the anti-tumor necrosis factor (TNF)-alpha chimeric monoclonal antibody infliximab in combination with corticosteroids only. The standard treatment containing cyclophosphamide has reduced the former high mortality from systemic vasculitides. However, the toxicity of this alkylating agent limits its long-term use. As TNF-alpha has been shown to play a central pathogenic role in vasculitis as well as in crescentic glomerulonephritis, anti-TNF-alpha treatment in combination with cyclophosphamide has been found to be effective in therapy-resistant vasculitis. Previous reports on TNF-alpha-blocking therapies without additional cyclophosphamide did not include patients with active and severe crescentic glomerulonephritis. As our patient refused cyclophosphamide, he was given four infusions of infliximab (4 mg/kg on weeks 0, 2, 6 and 10) and methylprednisolone pulses (1 g on days 1-3), followed by daily oral prednisolone (starting with 2 mg/kg and tapering down to 5 mg daily within 3 months). After 12 weeks, control biopsy demonstrated lack of active glomerular inflammation while initially reduced renal function (creatinine 271 versus 172 mol/l, clearance 26 versus 62 ml/min) and proteinuria (2.4 versus 1.0 g/d) improved. Under remission maintenance therapy with azathioprine and prednisolone, the patient showed no relapses during a 1-year follow-up. Finally we demonstrate that there might be patients with crescentic glomerulonephritis who do not require therapy with alkylating substances and that less toxic agents such as the TNF-alpha-blocking monoclonal antibody infliximab could play a role in future primary treatment of crescentic glomerulonephritis.

Post-transplant lymphoproliferative disease (PTLD) is a serious complication after organ transplantation. We describe the case of a 45-year old patient who developed an EBV associated B-cell lymphoma in a cadaveric renal allograft. This case underscores the importance of considering PTLD as possible differential diagnosis for allograft dysfunction. Careful diagnostic evaluation should be undertaken in patients who present with risk factors for development of PTLD such as high doses of immunosuppression for rejection therapy, suspicious EBV serologies or negative EBV serologies before transplantation. PTLD can be of donor or recipient origin. Independent of its origin PTLD needs an immediate therapy which depends on the histology of the lymphoma and on the clinical conditions of the patient. Therapeutic options are reduction of the immunosuppression, chemotherapy or radiation, administration of lymphocyte-specific antibodies or removal of the kidney allograft.

Wir schildern 2 Falle mit Glomerulonephritis Typ Minimallasion (Synonyme: Minimal Change Glomerulonephritis (MCGN), idiopathisches nephrotisches Syndrom). Eine 47-jahrige Patientin stellte sich mit einem seit der Kindheit bestehenden, rezidivierenden nephrotischen Syndrom bei uns vor. Eine weitere, 22-jahrige Patientin wurde zu uns wegen Infektanfalligkeit seit einem Jahr sowie zunehmenden Beinschwellungen seit einigen Monaten uberwiesen. Die in beiden Fallen vermutete Minimal Change Glomerulonephritis kann nur mittels Nierenbiopsie elektronenmikroskopisch bewiesen werden. Die therapeutischen Moglichkeiten sind Steroide, Ciclosporin, Tacrolimus oder gar Cyclophosphamid, abhangig vom Verlauf der Krankheit bei diesen beiden Patientinnen.

Eosinophilic fasciitis (EF) is characterized by symmetrical scleroderma-like induration of skin over one or more distal extremities, peripheral eosinophilia, absence of Raynaud phenomenon and visceral involvement and a favourable response to systemically administered corticosteroids. Like other scleroderma-like disorders EF is rarely described in children. We report renal involvement in a 17-year-old boy with EF. Urinalysis disclosed proteinuria. Prior to corticosteroid therapy renal biopsy was performed which revealed ischemic collapse of glomerular capillaries and atrophy of tubules of the cortex. Electron-microscopic studies showed hyperplasia of the renin-producing epitheloid cells in the juxtaglomerular apparatus. Few other publications have depicted renal involvement in EF of quite different character. In these cases renal biopsy and histological classification is warranted because of prognostic and therapeutic implications.

Leptin inhibits food intake and increases energy expenditure. Although the kidney expresses abundant transcripts of the short form of the leptin receptor (Ob-Ra), a role for this hormone in renal function remains unclear. Because individuals with massive obesity who may exhibit increased leptin serum concentrations develop renal glomerulosclerosis, we studied whether leptin can influence renal growth and profibrogenic processes.The effects of recombinant leptin on proliferation and synthesis of transforming growth factor-beta1 (TGF-beta1) was investigated in cultured glomerular endothelial cells of the rat (GERs) and syngeneic mesangial cells. Furthermore, leptin receptor expression and potential signal transduction pathways were evaluated in GERs. In addition, leptin was also infused for different time periods (72 hr and 3 weeks) into naive rats.Recombinant mouse leptin induced proliferation of GERs, but not of syngeneic mesangial cells. Coincubation with angiotensin II and leptin exerts additive proliferative effects in GERs. An antileptin-receptor antibody totally abolished this proliferation but did not influence serum-induced proliferation. GER expressed high affinity receptors of the Ob-Ra type (Kd, 4 nM; Bmax, 9700 receptors/cell). Leptin also stimulated phosphorylation of STAT1alpha, and kinase inhibitors attenuated proliferation, suggesting a pivotal role of phosphorylation in this process. Incubation of GERs with leptin also induced mRNA expression of TGF-beta1 and enhanced secretion of this profibrogenic cytokine. Short-term leptin infusion (72 hr) into naive rats induced a significant proliferation, mainly restricted to glomerular endothelial cells, and enhanced glomerular TGF-beta1 mRNA levels. In rats continuously infused for three weeks with leptin, glomerular TGF-beta1 expression was still enhanced, and an additional increase in glomerular collagen type IV mRNA and protein expression was detected. These animals revealed an increase in proteinuria compared with control-infused rats.Our findings are the first in vitro and in vivo demonstration that leptin is a renal growth and profibrogenic factor. These results may be an important contribution to our understanding of how leptin can contribute to renal damage, characterized by endocapillary proliferation and subsequent development of glomerulosclerosis, in pathophysiological situations with high circulating levels such as in diabetics or obese individuals. Although the effects of leptin itself are moderate, growth-promoting and profibrogenic effects may be enhanced in concert with other factors such as angiotensin II.

Because of their oxygen binding capacity, cell-free hemoglobin solutions are promising blood substitutes. However, their clinical use has so far been limited by toxic side effects on liver and kidney until ultrapurification and chemical modifications have been established in the production process of hemoglobin-based oxygen carriers. The present study has been designed to examine structural changes of liver and kidney by light and electron microscopy after complete isovolemic blood exchange with a new ultrapurified bovine hemoglobin solution (UPBH-2) in eight beagle dogs. The results have been compared with a sham-operated control and eight animals having undergone blood exchange with hydroxyethyl starch (HES), a clinically used colloidal volume substitute. In the kidney, no changes were observed after blood exchange with UPBH-2 as compared with the sham control. These findings indicate sufficient tissue oxygenation and lack of renal toxicity. In contrast, histological signs of severe proximal tubular damage, eg, wide lumina, cytoplasmic protrusions, brush-border defects, and tubular necroses, were seen after blood exchange with HES. These changes are consistent with hypoxic tissue damage. In the liver, a slight increase in the number of single cell necroses was observed after UPBH-2 treatment as well as after blood exchange with HES. At the ultrastructural level, partial loss of microvilli and cytoplasmic protrusions of hepatocytes as well as swelling of endothelial cells were present in both groups, but slightly more pronounced in the UPBH-2 group. In all UPBH-2-treated animals, a marked diminution of glycogen-granula in hepatocytes was observed indicating an influence of UPBH-2 upon glycogen metabolism. Whereas the alterations of hepatocytes after nearly complete blood exchange with HES can be interpreted as a consequence of tissue hypoxia, the ultrastructural changes after UPBH-2 treatment cannot be attributed to hypoxic conditions, because improved tissue oxygenation has been demonstrated during treatment with UPBH-2. Hepatocyte damage was very discrete and comparable with the alterations observed after HES treatment. Hence, major hepatotoxicity can be excluded. The absence of significant adverse effects on the ultrastructural integrity of the kidney indicates that UPBH-2, owing to ultrapurification and polymerization, is an oxygen-carrying hemoglobin without acute renal toxicity.

An 82-year-old woman with hypertension for 20 years developed a nephrotic syndrome with severe oedema followed by acute oliguric renal failure after a bout of bronchitis and a gastrointestinal infection. She also complained of xerostomia and dry eyes of recent onset.Biochemical tests showed a serum creatinine level of 6.1 mg/dl, a 1:5120 antinuclear antibody (ANA) titre, and positive values for Ro(SS-A) and La(SS-B) antibodies. HLA-DR typing demonstrated HLA-DR3 (HLA-DRB1*0301) and DR13 (HLA-DRB1*13) antigens. Renal biopsy revealed minimal glomerular lesions with focal and segmental glomerulo-sclerosis as well as (hypertension-induced) benign nephrosclerosis and focal tubular atrophy with interstitial fibrosis.After two hemofiltrations and concomitant administration of 100 mg prednisone renal function quickly improved and the proteinuria fell to 1 g/dl. At the same time the xerostomia improved. The nephrotic syndrome recurred 7 months later after the prednisone dose had been reduced to 10 mg/d, but after the dose had been raised to 50 mg/d and cyclosporin A (150 mg/d) had been added a lasting remission occurred and renal function became stable though impaired.The relatively rare association of glomerular disease (here focal segmental glomerulosclerosis) with Sjögren's syndrome can, as in this case, be triggered by a viral infection. A genetic predisposition for Sjögren's syndrome is suggested by the demonstration of HLA-DR3 alleles. Administration of steroids is indicated for the treatment of the nephrotic syndrome and, in case of recurrence, can be combined with cyclosporin A. Both drugs also influence the symptoms of Sjögren's syndrome.