Dieter Bach

Nephrotoxicity of cyclosporine in humans: effect of cyclosporine on glomerular filtration and proximal tubular reabsorption

SummaryThe chronic nephrotoxic effects of cyclosporine (CsA) include proximal tubular atrophy and vacuolization. This study investigated the effect of CsA on renal hemodynamics and segmental electrolyte transport in CsA-treated patients. The clearance of inulin (CIn) and PAH para-amino-hippuric acid (CPAH) was determined; proximal tubular function was studied using a lithium clearance method and calculating tubular phosphate reabsorption per milliliter of glomerular filtrate (TP/CIn). Twenty patients without renal disease were investigated: ten treated with CsA because of nonrenal grafting (group 1) and ten healthy volunteers (group 2). The results obtained were compared with those from 20 renal allograft recipients, of whom ten were treated with CsA and methylprednisolone (group 3) and ten with azathioprine and methylprednisolone (group 4). CIn and CPAH were significantly impaired in patients treated with CsA. No significant impairment of lithium clearance as induced by CsA was observed. The fractional excretion of lithium was slightly increased in patients treated with CsA compared to their respective controls. TP/CIn was lower in graft recipients compared to controls; no impairment of phosphate reabsorption as induced by CsA was found. The fractional tubular excretion of lithium was slightly increased compared to controls, rising evidence that proximal tubular reabsorption of lithium was decreased. Tubular reabsorption of phosphate was not impaired. The decrease in glomerular filtration and renal perfusion during chronic treatment with CsA was accompanied by a reduced proximal reabsorptive capacity, as was shown by lithium clearance. Our data do not support the hypothesis that functional parameters of the proximal tubular system can be used as indicators of CsA-induced nephrotoxicity.

The German Glomerulonephritis Therapy Study: 10 Years of Controlled Randomized Trials for the Treatment of Idiopathic Glomerulonephritis

The German Collaborative Glomerulonephritis Therapy Study, which celebrated its 10th anniversary in 1996, has collected data on more than 1,000 patients with biopsy-proven glomerulonephritis. 929 patients could be evaluated and 500 were treated according to at least one of various protocols developed for a randomized controlled trial. Current results show that prednisolone is effective in minimal-change nephropathy, and in combination with other immunosuppressants it can reduce proteinuria in individual cases of focal and segmental glomerulosclerosis, membranous glomerulonephritis and nephrotic IgA nephropathy. The majority of tested treatment protocols did not prove to be superior to symptomatic therapy for long-term outcome.

Association of primary renal non-Hodgkin's lymphoma with mesangioproliferative glomerulonephritis

A 27‐year‐old male developed nonoliguric renal failure. Renal biopsy of the left kidney showed infiltration by a diffuse large‐cell non‐Hodgkins lymphoma (NHL). Laparoscopy, CT scans of the abdomen and thorax, and bone‐marrow biopsy revealed no further manifestations of lymphoma. Primary renal NHL was diagnosed. The patient attained complete remission with cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP) chemotherapy and remained disease‐free for 13 years. Eight years after his first presentation, the patient developed acute oliguric renal failure with nephrotic syndrome. Mesangioproliferative glomerulonephritis was diagnosed in a biopsy of the left kidney. Chronic hemodialysis was required until cadaver kidney transplantation was successfully performed 5 years later. Although the association of NHL and glumerulonephritis has been described several times before, to our knowledge this is the first report of glomerulonephritis in primary renal lymphoma.

Influence of Mycophenolic Acid and FK–506 on Human Platelet Activation in vitro

Background/Aim: FK–506 (FK) and mycophenolic acid (MPA) are immunosuppressive agents used in kidney transplant recipients. Their effect on posttransplant thromboembolic complications is either controversial (FK) or has not been described (MPA). Thromboembolic events are among the consequences of platelet hyperaggregability which can be identified by measuring platelet aggregation. The aim of this study was to evaluate the in vitro effects of MPA and FK upon platelet activation in healthy subjects. Methods: Platelet–rich plasma from healthy volunteers (n = 18) was incubated with FK (70 ng/ml), FK vehicle, and MPA (30 μg/ml) before platelet aggregation was induced by the platelet agonists adenosine diphosphate (2 and 5 μM) and collagen 0.5 and 1.0 μg/ml). Aggregation was measured by recording the optical density. Results: MPA resulted in a significant decrease in the platelet response to collagen (1.0 μg/ml) in platelet–rich plasma, whereas FK significantly increased platelet aggregation in response to collagen (0.5 μg/ml). The vehicle of FK had no influence on platelet aggregation with either agonist. Conclusions: The decreased platelet–activating response following preincubation with MPA may favor its use in kidney transplant recipients to reduce thromboembolic events. The FK–induced enhancement of platelet aggregation shown in vitro may lead to thromboembolic complications in transplant recipients.

Immunsuppression in der Therapie der Glomerulonephritis

Zum ThemaBei den überwiegend immunpathogenetisch bedingten Glomerulonephritiden (GN) unterscheidet man primäre und sekundäre Formen. Die primären Formen sind durch fehlende, die sekundären durch vorhandene andere Systemerkrankungen definiert. Durch ihre Immunpathogenese sind die Glomerulonephritiden prädestiniert für eine immunsuppressive bzw. - modulierende Therapie.Darüber gibt die vorliegende Arbeit einen Überblick. Sie enthält gleichzeitig eine Klassifikation der GN unter klinischen und der rasch progressiven GN unter immunpathogenetischen Gesichtspunkten und beschäftigt sich außerdem mit den Ursachen des nephrotischen Syndroms.

Die Ciguatera-Vergiftung

Zusammenfassung□ HintergrundIn tropischen Meeren kommen karnivore Speisefische wie der Zackenbarsch vor, die bestimmte toxinbildende Algen enthalten und eine Ciguatera-Vergiftung auslösen könne. Wegen des gehäuften Fernreisetourismus in die tropische Zone treten in Europa immer mehr Fälle von Ciguatera-Vergiftungen auf. Diese Vergiftung ist in ihrem Spätstadium wegen der vielfältigen, uncharakteristischen Symptomatik differentialdiagnostisch schwer zu erkenen. In seltenen Fällen kann die Ciguatera-Vergiftung auch zur vitalen Gefährdung der betroffenen Patienten werden.□ FallbeschreibungVier Patienten aus einer Reisegruppe stellten sich vier und 14 Tage nach Abbruch ihres Karibikurlaubs mit einer komplexen neurologischen Symptomatik vor, welche aus Parästhesien, Unruhe, inversem Temperaturempfinden, Muskelkrämpfen, Zephalgien und Schwindel bestand. Die körperliche und apparative Untersuchung der Patienten im Alter zwischen 22 und 33 Jahren war völlig unauffällig. Wegweisend für die Diagnose einer Ciguatera-Vergiftung war der Hinweis auf ein auslösendes Abendessen mit Zackenbarsch in Limonensoße am Urlaubsort, das zunächst bei allen Mitgliedern der Reisegruppe Durchfall, Übelkeit und Schweißausbrüche auslöste. Es konnte in diesem Spätstadium nur noch eine symptomatische Therapie angeboten werden.□ SchlußfolgerungDie geschilderten Fallbeispiele zeigen die Bedeutung einer umfassenden Information von Tropenreisenden wie von in der Akutphase konsultierten Ärzten über Ciguatera-Vergiftung, denn bei rechtzeitiger Diagnose innerhalb der ersten 24 Stunden kann der gesamten Symptomatik durch intravenöse Mannitolinfusionen effektiv vorgebeugt werden.Abstract□ BackgroundIn the tropic sea there are carnivore fishes, e. g. the “peak bass”, that incorporate toxin producing seaweed and can cause the ciguatera intoxication. Due to the frequent tourism to tropic regions even more cases of ciguatera intoxication can be seen in Europe. The late phase of ciguatera intoxication has hardly been recognized due to its different unspecific symptoms. In some cases ciguatera intoxication can even grow a vital threatening.□ Case DescriptionFour patients from a travel group addressed us 4 and 14 days after breaking off their holidays in the Dominican republic. They presented complex neurological symptoms including paraesthesia, nervousness, inverse temperature perception, muscle cramps, headache and dizziness. The physical and apparative investigation of the patients, whose age ranked between 22 and 31 years, was totally unobtrusive. Essential for the diagnosis of ciguatera intoxication was the clue to the symptom causing dinner at their holiday location existing of “peak bass and lemon sauce”. First symptoms in all members of the travel group were diarrhea, sickness and sweatening. In this late phase only a symptomatic therapy could be offered.□ ConclusionThe here described cases show the importance of a comprehensive information for tropic travellers as for physicians accounted to in the acute phase of ciguatera intoxication, because recognized early enough (within the first 24 hours) the total symptomatology of ciguatera intoxication can be prevented effectively by intravenous infusions of mannitol.

Glomerulonephritis und malignes Lymphom

BACKGROUND The association of non-Hodgkins lymphoma with different types of glomerulonephritis is well-known for many years. Whereas in Hodgkins disease, minimal change glomerulonephritis is mainly observed, in non-Hodgkins lymphoma various forms of glomerulonephritis are found. PATIENTS AND RESULTS We describe 3 cases of non-Hodgkins lymphoma, which were associated with glomerulonephritis. Two cases of glomerulonephritis showed nephrotic syndromes, which improved by medicinal treatment. In 2 cases glomerulonephritis and non-Hodgkins lymphoma developed simultaneously. In a third lymphoma was followed by glomerulonephritis after 3 years. CONCLUSION Although the pathogenetic relationship between non-Hodgkins lymphoma and glomerulonephritis is not fully understood, the high number of reported cases yield interdependence. Lymphoma associated glomerulonephritis is found more often in men than in women. Low-grade non-Hodgkins lymphomas--especially chronic lymphatic leukemias--seem to develop glomerulonephritis more frequently than high-grade. The majority of non-Hodgkins lymphoma do not show any predisposition to a special type of glomerulonephritis, only in cutaneous lymphoma IgA-nephropathy predominates.Zusammenfassung□ HintergrundGleichzeitiges Vorkommen von malignen Lymphomen und verschiedenen Glomerulonephritisformen ist lange bekannt. Während aber die Hodgkinsche Erkrankung oft zusammen mit “Minimal-change”-Glomerulonephritis auftritt, finden sich bei den Non-Hodgkin-Lymphomen ganz unterschiedliche Glomerulonephritisformen.□ Patienten und ErgebnisseEs werden drei Fälle von Non-Hodgkin-Lymphomen mit unterschiedlichen Glomerulonephritiden beschrieben. Zwei Glomerulonephritiden gingen mit nephrotischem Syndrom einher, das sich unter symptomatischer Behandlung besserte. In zwei Fällen manifestierten sich Glomerulonephritis und Non-Hodgkin-Lymphom gleichzeitig, im dritten Fall trat die Glomerulonephritis erst drei Jahre nach der Lymphomdiagnose auf.□ SchlußfolgerungAus diesen und in der Literatur belegten Fällen läßt sich schließen, daß die Vielzahl beschriebener Syntropien für Abhängigkeiten zwischen Non-Hodgkin-Lymphomen und Glomerulonephritis spricht. Bei Männern scheint die Assoziation häufiger zu sein. Niedrigmaligne Non-Hodgkin-Lymphome, insbesondere chronische lymphatische Leukämien, gehen häufiger mit Glomerulonephritis einher als hochmaligne Formen. Selten weisen Non-Hodgkin-Lymphome eine Bevorzugung bestimmter Glomerulonephritistypen auf. Lediglich kutane Non-Hodgkin-Lymphome gehen häufiger mit IgA-Nephritiden einher. Die pathogenetischen Zusammenhänge einer Syntropie von malignen Lymphomen und Glomerulonephritiden sind allerdings bisher nur unzureichend geklärt.Summary□ BackgroundThe association of non-Hodgkin’s lymphoma with different types of glomerulonephritis is well-known for many years. Whereas in Hodgkin’s disease, minimal change glomerulonephritis is mainly observed, in non-Hodgkin’s lymphoma various forms of glomerulonephritis are found.□ Patients and ResultsWe describe 3 cases of non-Hodgkin’s lymphoma, which were assoicated with glomerulonephritis. Two cases of glomerulonephritis nephritis showed nephrotic syndromes, which improved by medicinal treatment. In 2 cases glomerulonephritis and non-Hodgkin’s lymphoma developed simultaneously. In a third lymphoma was followed by glomerulonephritis after 3 years.□ ConclusionAlthough the pathogenetic relationship between non-Hodgkin’s lymphoma and glomerulonephritis is not fully understood, the high number of reported cases yield interdependence. Lymphoma associated glomerulonephritis is found more often in men than in women. Low-grade non-Hodgkin’s lymphomas — especially chronic lymphatic leukemias — seem to develop glomerulonephritis more rrequently than high-grade. The majority of non-Hodgkin’s lymphoma do not show any predisposition to a special type of glomerulonephrits, only in cutaneous lymphoma IgA-nephropathy predominates.

Renal functional reserve in patients with IgA glomerulopathy.

UNLABELLED Seven patients with histologically proven IgA nephropathy and modest impairment of renal function, and 2 patients with IgA nephropathy and nephrotic syndrome were investigated, compared to a control group of 9 healthy individuals, to study the effects of amino acids on glomerular and tubular function, and to evaluate renal functional reserve in IgA nephropathy with different clinical course. Inulin and PAH clearances were used to evaluate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF); proximal and distal tubular fluid delivery and reabsorption were measured by lithium clearance, before and after submission of a standardized amino acid solution. GFR and ERPF increased significantly during amino acid load in healthy individuals and patients without nephrotic syndrome, while filtration fraction (GFR/ERPF) remained constant. Lithium clearance (CLi) and fractional lithium excretion (CLi/GFR) rose significantly in both groups, whereas the reabsorbed volume of fluid in the proximal tubule did not change. In the distal tubule, fractional volume excretion decreased significantly during amino acid load whereas the reabsorbed volume significantly increased. Baseline values of the two groups did not differ significantly. Two patients with nephrotic course of IgA nephropathy showed a distinct decrease in glomerular and tubular function, and a loss of renal functional reserve after amino acid load. CONCLUSIONS Despite distinct alterations in renal biopsy, IgA nephropathy without nephrotic course presents with a still adequately preserved kidney function and renal functional reserve. A single determination of renal function with noninvasive functional tests does not give valid prognostic information concerning glomerular and tubular function. Therefore, a repeated measurement of renal function at defined intervals might reveal clinical progression of renal disease. The results of the lithium clearance might indicate an increase in tubular function after amino acid load, indicating a tubular adaptation in state of hyperfiltration.