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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.

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.

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.

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.

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.

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.

We have recently shown that treatment with the calcium channel blocker nitrendipine may aggravate albuminuria and glomerular injury in rats with two-kidney, one clip renovascular hypertension if arterial blood pressure is not reduced. To test whether nitrendipine also exerts its adverse renal effects when normotension is achieved, we examined the effect of combined therapy with nitrendipine and the converting enzyme inhibitor enalapril on blood pressure, albuminuria, glomerular filtration rate, and morphology of the nonclipped kidney. Rats treated with enalapril alone or in combination with the diuretic hydrochlorothiazide or rats treated with nitrendipine alone served as controls. Therapy was started 6 weeks after clipping of one renal artery. Nitrendipine alone did not reduce blood pressure but significantly increased albuminuria, diuresis, glomerular filtration rate, and glomerular volume and injury compared with untreated hypertensive controls. Increase of glomerular filtration rate, diuresis, and albuminuria was reversible after withdrawal of nitrendipine. Treatment with enalapril alone decreased blood pressure significantly but not to normotensive levels and was without significant effect on albuminuria and glomerular morphology. The combination of nitrendipine and enalapril reduced blood pressure to normotensive levels and not only prevented the increase of glomerular volume, glomerular filtration rate, diuresis, and albuminuria caused by nitrendipine alone but furthermore improved glomerular injury and albuminuria to levels not significantly different from normotensive controls. Enalapril in combination with the diuretic had similar beneficial effects on blood pressure, albuminuria, and glomerular injury. These data demonstrate that the adverse effects of nitrendipine monotherapy on glomerular structure and function can be prevented by the combination of nitrendipine and enalapril when blood pressure is normalized.

The effect of a 6-week treatment with the calcium channel blocker nitrendipine or the angiotensin converting enzyme inhibitor enalapril on blood pressure, albuminuria, renal hemodynamics, and morphology of the nonclipped kidney was studied in rats with two-kidney, one clip renovascular hypertension. Six weeks after clipping of one renal artery, hypertensive rats (178 +/- 4 mm Hg) were randomly assigned to three groups: untreated hypertensive controls (n = 8), enalapril-treated (n = 8), or nitrendipine-treated (n = 10). Sham-operated rats served as normotensive controls (128 +/- 3 mm Hg, n = 8). After 6 weeks of treatment, renal hemodynamics (glomerular filtration rate and renal plasma flow) were measured in the anesthetized rats. Renal tissue was obtained for determination of glomerular size and sclerosis. Enalapril but not nitrendipine reduced blood pressure significantly. After 6 weeks of therapy, glomerular filtration rate was not different among the studied groups. Renal plasma flow increased, but albumin excretion and glomerulosclerosis did not change after enalapril treatment. In contrast, in the nitrendipine-treated group albuminuria increased from 12.8 +/- 2 progressively to 163 +/- 55 compared with 19.2 +/- 9 mg/24 hr in the hypertensive controls. Furthermore, glomerulosclerosis index was significantly increased in the nitrendipine-treated group compared with the hypertensive controls (0.38 +/- 0.1 versus 0.13 +/- 0.04). In addition, glomerular size was higher in the nitrendipine-treated group (14.9 +/- 0.17 10(-3) mm2) but lower in the enalapril-treated group (11.5 +/- 0.15 10(-3) mm2) compared with the hypertensive controls (12.1 +/- 0.17 10(-3) mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

Renal biopsy specimens of 40 patients with recent-onset insulin-dependent diabetes mellitus treated with cyclosporine (CSA) for 6-29 months were examined. Cyclosporine-associated chronic vascular interstitial toxicity of moderate intensity was found in 10 patients (25%). The most prominent lesions were interstitial fibrosis and tubular atrophy. Arteriolopathy was less pronounced and glomerular damage unremarkable. A significant correlation exists between the extent of tubular atrophy and CSA trough whole blood levels. These data indicate that the development of CSA-associated chronic nephropathy is dose-dependent.

So far two methods for prolonging the tolerance of renal ischemia are available: 1) surface cooling with crushed ice and 2) perfusion cooling with an extracellular-like solution. Both methods use only the principle of reducing metabolism through cooling. While rewarming during surgery the ischemic protection is lost, or the kidney must be cooled once again. Therefore, a new preservation solution should reduce energy consumption due to its composition in addition to cooling. For open heart surgery, the HTK solution by Bretschneider is already used clinically. In 71 dog kidney experiments, the ischemic time kidneys could tolerate was prolonged by this solution from 15 to 120 min at 35 degrees C and from 45 to 360 min at 25 degrees C. After 2 h of ischemia at 30 degrees C glomerular filtration rate was about 20 ml/min.100gww within 3 h of reperfusion. After six postoperative days the filtration rate was 40 ml/min.100 gww. No ischemic damage could be recognized by histological investigations. The clinical effectiveness of this method was shown in 7 clinical applications. Ischemic duration lasted up to 113 min, and blood creatinine was between 0.8 and 2.4 mg% at the 6th postoperative day. Use of this preservation technique thus leads to improved kidney function immediately following operation. Longer ischemia can be tolerated by a kidney thus protected, and using this technique excellent visibility can be achieved during intrarenal surgery, simplifying, for example, tumor extirpation.

Pathogenese und Mechanismen der Progression chronischer Glomerulonephritiden (GN) sind bisher nicht geklart. Dennoch gibt es erfolgversprechende, prospektive, kontrollierte Therapie-Studien sowie neue Therapie-Ansatze. So wurden beispielsweise Patienten mit idiopathischermembranoser GN monatlich mit Chlorambucil (0,2 mg/kg/Tag) oder Prednison (0,6 mg/kg/Tag) im Wechsel uber sechs Monate behandelt. Im Vergleich zu den unbehandelten zeigte sich bei den behandelten Patienten innerhalb von drei Jahren ein gunstiger Verlauf der Nierenfunktionsparameter. In einer anderen Studie erhielten Patienten mitmembrano-proliferativer GN Typ I uber ein Jahr taglich 975 mg Aspirin und 225 mg Dipyridamol. Bei den behandelten trat im Gegensatz zu den nichtbehandelten Patienten eine Stabilisierung der Nierenfunktion und eine Normalisierung der vorher beschleunigten Thrombozyten-Uberlebensrate ein. In einer weiteren kontrollierten Therapie-Studie wurde gezeigt, das die Langzeit-Prognose derdiffus-proliferativen Lupus-Nephritis (Typ IV WHO) besser ist, wenn eine kombinierte Behandlung mit Cyclophosphamid (100 mg/Tag) und Prednison (30 mg/Tag) uber mehrere Monate erfolgt als eine alleinige Prednison-Behandlung (40 mg/Tag).

In a pilot study 23 children with nephrotic syndrome were treated with cyclosporin A (Cs) for 6-45 months. 8 children suffered from steroid dependent minimal change nephrotic syndrome (MCNS) and had experienced at least one course with cytotoxic drugs, but had relapsed thereafter. 2 children had diabetes mellitus type I with nephrotic syndrome and 13 children had steroid resistant focal segmental glomerulosclerosis (FSGS). Cs was started with 100 mg/m2/day in two doses and increased stepwise to obtain a Cs whole blood trough level of 200-400 ng/ml. In steroid dependent MCNS treatment with Cs reduced relapse rate significantly, and prednisone therapy could be stopped completely. After discontinuation of Cs, relapses reoccurred as frequently as before. Renal function remained unimpaired despite repeated Cs treatment courses up to 38 months. In cases of nephrotic syndrome with diabetes type I Cs treatment led to complete remission without changing the insulin requirement. However, after discontinuation of Cs relapses reoccurred. In steroid resistant FSGS 6 children benefited from Cs treatment: 4 went into complete remission, 2 into partial remission. The 2 children with complete remission relapsed but remained Cs responsive. The remaining 7 children with FSGS did not respond to Cs but continued the course of their disease, with two patients rapidly progressing to terminal renal failure. Side-effects of Cs treatment were mild. It is concluded that Cs is an effective agent in steroid dependent MCNS and can be used as an alternative drug in specific cases like steroid toxicity or diabetes mellitus. In steroid resistant FSGS a trial with Cs seems to be warranted since some cases do respond favorably. To avoid nephrotoxicity treatment with Cs should always be monitored closely by determination of blood levels and renal function.

We report light- and electron microscopic findings in glomerular amyloidosis (secondary amyloidosis), which occurred after recurrent empyema of the pleura. After healing of the empyema, the clinical symptoms disappeared, over a period of eight years. During the acute stage of the disease (grade II-III amyloidosis) when the nephrotic syndrome was present, amyloid deposits were seen in the mesangium and on both sides of the basement membrane of the glomerular capillaries. Furthermore, denuded basement membrane areas showing the passage of amyloid into the urinary space, and invaginations of the podocyte by straightened amyloid fibrils were found. After clinical recovery (except for a trace of proteinuria), the renal amyloidosis had electronmicroscopically transformed from an active into an inactive or resting form, while the amount of amyloid present was almost the same. In the areas of amyloid deposits, reparative changes were observed, espcially in the area of the mesangial cells and of the podocytes. The podocytes were separated from the persisting amyloid deposits by newly formed basement membrane material.

Veno-occlusive disease (VOD) developed in a 4 5-year-old white male 2 years after cadaveric kidney transplantation while receiving combined immunosuppressive therapy with prednisone and azathioprine.

Die Untersuchung der Nieren von 54 Patienten mit maligner Nephrosklerose ergab, das aufgrund unterschiedlicher morphologischer und klinischer Befunde eine Differenzierung dieses Krankheitsbildes in zumindest 2 Gruppen erforderlich ist. Bei der ersten Gruppe handelt es sich um Patienten, bei denen sich die maligne Nephrosklerose sekundar im Verlauf einer meist mehrjahrigen Hochdruckanamnese entwickelt hatte. Bei der zweiten Gruppe gingen die fur die maligne Nephrosklerose kennzeichnenden renalen Gefasveranderungen, zumindest in einigen Fallen (5 von 22), der malignen Hypertonie voraus. Die letztere Form der malignen Nephrosklerose wird als primare maligne Nephrosklerose von der hochdruckbedingten sekundaren malignen Nephrosklerose abgegrenzt. Von klinischer Seite mus der Verdacht auf eine primare maligne Nephrosklerose geausert werden, wenn sich, meist nach uncharakteristischem Infekt, sehr schnell eine Niereninsuffizienz im Sinne des akuten Nierenversagens mit schwerer Anamie bei normalem oder erhohtem Blutdruck entwickelt. Eine progrediente Entwicklung einer Niereninsuffizienz in mehreren Wochen bzw. Monaten bei Bestehen eines Hypertonus spricht dagegen fur eine sekundare maligne Nephrosklerose. Durch Analyse der vascularen Lasionen bei den beiden Formen der malignen Nephrosklerose konnte gezeigt werden, das bei der primaren malignen Nephrosklerose die Vasa afferentia im Durchschnitt haufiger erkrankt sind als bei der sekundaren malignen Nephrosklerose. Die Akuitat des Krankheitsverlaufes bei primarer maligner Nephrosklerose bringt es daruber hinaus mit sich, das bei dieser Erkrankung akute, oft mit Thrombenbildungen einhergehende Gefaswandschaden dominieren, wahrend bei der sekundaren malignen Nephrosklerose die chronischen Gefaswandlasionen (z. B. produktive Endarteriitis Fahr) starker hervortreten. Daruber hinaus ergaben unsere Untersuchungen, das die primare maligne Nephrosklerose bei im Durchschnitt jungeren Patienten auftritt als die sekundare maligne Nephrosklerose, ferner, das an der primaren malignen Nephrosklerose uberwiegend Frauen, an der sekundaren malignen Nephrosklerose vorwiegend Manner erkranken. Die Beziehungen zwischen primarer maligner Nephrosklerose und dem hamolytisch-uramischen Syndrom Gasser werden aufgezeigt. Ferner wird eine Abgrenzung der primaren malignen Nephrosklerose vom Moschcowitz-Syndrom, vom generalisierten Shwartzman-Phanomen sowie von der sog. mikroangiopathischen hamolytischen Anamie versucht.

Plasma renin activity was estimated in normal and in renal hypertensive rats, in the unanesthetized state, in ether or in urethane anesthesia. Renal hypertension was induced by partially constricting one renal artery without touching the opposite kidney. In the unanesthetized state plasma renin activity in renal hypertensive rats was slightly, though very variably, increased (∼45 percent). Ether anesthesia had no influence on plasma renin activity in either normotensive or hypertensive rats. Urethane anesthesia lowered blood pressure in normotensive controls by 20 mm Hg, and caused a more than threefold increase in plasma renin activity. In renal hypertensive rats urethane depressed blood pressure by 40 mm Hg and induced a more than sixfold increase of plasma renin activity.

Renovascular hypertension does not influence repair of glomerular lesions induced by anti-thymocyte glomerulonephritis. Background Systemic hypertension is a risk factor for progression of renal disease. However, it is not clear whether hypertension has an effect on healing or regression of immune-mediated glomerular damage. To evaluate this effect, we applied a model of glomerulonephritis in rats with two-kidney, one-clip hypertension and studied the effect of hypertension on the healing process of this nephritis. Methods The anti-thymocyte serum (ATS) glomerulonephritis was induced in rats six weeks after initiation of two-kidney, one-clip hypertension, when blood pressure was already increased. Renal structure and function were examined six weeks later. Glomerular expression of α smooth muscle actin, the cell cycle inhibitor p27 Kip1 , and transforming growth factor-β (TGF-β) was evaluated by Western blotting. Glomerular proliferation, monocyte infiltration, and fibronectin were examined by immunohistochemistry. Results Decreased survival, an increase of proteinuria, as well as increased glomerular and tubulointerstitial damage, were found in hypertensive rats compared with normotensive rats. Expression of fibronectin, α-smooth muscle actin, TGF-β, and p27 Kip1 was increased in the nonclipped kidney. Complete healing of the glomerular changes associated with the nephritis occurred in normotensive nephritic rats. Surprisingly, complete healing of the nephritis was also found in the clipped as well as nonclipped kidneys of renovascular hypertensive rats. No significant differences could be found for survival, proteinuria, glomerular size, proliferation, monocyte/macrophage infiltration, sclerosis, tubulointerstitial damage, as well as expression of α-smooth muscle actin, TGF-β, fibronectin, and p27 Kip1 between hypertensive rats with and without nephritis. Conclusion These data demonstrate that renovascular hypertension does not influence healing of the glomerular lesions in the anti-thymocyte serum nephritis. This is a rather surprising observation and leaves the question open of which role, in fact, blood pressure may have on the reparative phase of an acute glomerulonephritis, or whether its role depends on the type of glomerulonephritis.

The C57BL/6 mouse strain serves as the genetic background of many transgenic and gene knockout models; however, this strain appears to be resistant to hypertension-induced renal injury. We developed a new model of hypertensive end-organ damage in C57BL/6 mice by combining deoxycorticosterone acetate (DOCA) and salt with angiotensin II infusion. The systolic blood pressure (SBP) was significantly elevated in DOCA salt-angiotensin II mice compared to control mice or mice treated individually with DOCA salt or angiotensin II. Hypertensive glomerular damage, increased expression of profibrotic and inflammatory genes, albuminuria, tubular casts, increased plasma cholesterol, cardiac hypertrophy, and fibrosis were found in mice treated with DOCA salt-angiotensin II. The SBP in the angiotensin II-infused group was further increased by increasing the infusion rate; only mild injury was observed in these mice, suggesting that blood pressure was not a causal factor. Removal of DOCA and the angiotensin pump lowered blood pressure to normal; however, albuminuria along with the glomerular and cardiac damage did not completely resolve. Our study describes a new model of hypertensive end-organ damage and repair in C57BL/6 mice.

1. As proposed by Schürmann & MacMahon (1933), we suggest that two types of malignant nephrosclerosis exist. 2. In the type called primary malignant nephrosclerosis, renal vascular lesions precede hypertension. 3. In the second type, called secondary malignant nephrosclerosis, renal vascular lesions are considered to be the consequence of malignant hypertension.

Eine einmalige intraperitoneale Furosemid-Gabe von 50–200 mg/kg KG fuhrt in der Rattenniere zu Epithelschaden im Bereich der pars recta des proximalen Tubulus. Diese tubularen Veranderungen treten nicht auf, wenn der Furosemid-induzierte Wasser- und Elektrolytverlust durch einen experimentell angelegten vesico-venosen Shunt verhindert wird. Die Tubuluszellschaden werden als Folge einer intracellularen Furosemid-Anreicherung bei vermindertem intratubularen Harnstrom angesehen.

In the presence of hypertension, the arterial and arteriolar vessel walls may undergo adaptive, destructive, and reparative changes. These different types of hypertensive alterations were studied simultaneously in the intrarenal vascular bed of two-kidney, one-clip hypertensive rats. After constriction of one renal artery, focal medial necrosis of the interlobular arteries developed in the untouched kidneys after the first 24 h. These earliest signs of vascular decompensation could be explained by short-lasting hypertensive episodes that were only detectable by continuous blood pressure recording in conscious animals. Two weeks after the experiment was started, owing to a widening of the media, a substantial increase in the wall-to-lumen ratio was observed in the interlobular arteries. At the same time, the frequency of focal medial necrosis began to fall significantly. Therefore we concluded that the structural vascular adaptation might be responsible for the disappearance of focal medial necrosis in spite of still rising blood pressure values. This assumption was confirmed by an additional experiment in previously chronically two-kidney, one-clip hypertensive rats: 24 h after removing the renal artery clip, a short, severely hypertensive period, induced by infusions of angiotensin II, caused hypertensive vascular lesions almost exclusively in the primarily clipped kidneys with a nonadapted vascular bed. Early intimal changes, which are known to lead to malignant nephrosclerosis, were not only absent in the beginning of two-kidney, one-clip hypertension, but also did not occur during the angiotensin-induced accelerated hypertension. Thus, even extremely high blood-pressure values per se may not be enough to initiate this crucial renal vascular disease.

We report on a 17 year old female patient with amenorrhea, hirsutism and slight acne. Hormonal blood analyses showed markedly increased levels for dehydroepiandrosteronesulfate, testosterone and androstenedione. Ultrasound investigation revealed a large tumor above the left kidney and a small area above the right kidney, suspicious for a tumor on the contralateral side. This was confirmed by angiography. During surgery, bilateral tumors were removed. Pathological diagnosis was made as bilateral adenomas of the adrenal cortex. Postoperatively, an impressive normalization was observed, accompanied by a rapid decrease of the elevated hormone concentrations. This case is the first report of a bilateral occurrence of a virilizing tumor of the adrenal cortex.

The cardioplegic solution HTK of Bretschneider was used for canine kidney protection. The kidneys were perfused with this solution for 6-10 min prior to the induction of ischemia. The kidneys were left in-situ for 60, 90, 120 and 135 min ischemia time at a temperature of 25-34 degrees C (n = 13). As a control group we used unilateral nephrectomized dogs (n = 9). After unilateral nephrectomy an elevated plasma creatinine in comparison to preoperative values was observed. After 60 and 90 min under HTK-protection the postoperative plasma creatinine was not elevated compared to the control group. After 120 min of ischemia creatinine level was slightly increased to an average of 2.1 mg% on the first and second postoperative day. These experiments indicate the protective effect of the cardioplegic solution for canine kidney preservation in situ.

The cardioplegia solution, HTK (histidine-tryptophan-ketoglutarate) (Bretschneider et al. 1975, 1984; Bretschneider 1980), was primarily developed to improve myocardial protection, as compared with periods of ischemia, during artificial cardiac arrest in open heart surgery. It has since become a routine clinical procedure (Preusse et al. 1987). According to our results, this solution also significantly improves ischemic tolerance of kidneys (Kallerhoff et al. 1985a, b, 1986, 1987c). The superiority over simple ischemia or over the Euro Collins solution holds for “cold” as well as for “warm” ischemia (Kallerhoff et al. 1988a). Renal ischemic tolerance was increased from 15–20 min to 2 h at normothermia (Kallerhoff et al. 1986). There have now been several clinical applications of this method (Blech et al. 1988; Kallerhoff et al. 1988b).