Late occurrence of cysts in autosomal dominant medullary cystic kidney disease.

Medullary cystic kidney disease (MCD) is characterized by multiple renal cysts at the corticomedullary boundary area, by autosomal dominant inheritance, and by onset of chronic renal failure in the third decade of life. We report on a family with three affected individuals of both sexes in two generations presenting with end-stage renal failure at age 22-31 years. Primarily diagnoses considered included unclassified hereditary nephropathy and autosomal dominant polycystic kidney disease. Careful evaluation of all findings, initiated after investigation of renal morphology with CT, revealed features characteristic for MCD and led to the final diagnosis of MCD. We conclude that MCD is an important differential diagnosis for polycystic kidney disease in young adults with end-stage renal failure. Establishing the correct diagnosis has considerable impact for genetic counselling.

[Unilateral diffuse pulmonary involvement in vasculitis with anti-neutrophil cytoplasmic antibodies and anti-glomerular basement membrane antibodies]. / Einseitige diffuse Lungenbeteiligung bei Vaskulitis mit Anti-Neutrophilen-Zytoplasma-Antikörpern sowie Antikörpern gegen glomeruläre Basalmembranen.

A previously healthy 51-year-old man, hospitalized because of fatigue and joint complaints, was found to have left-sided diffuse pulmonary infiltration and a rapid rise in creatinine concentration. Anti-neutrophil cytoplasmic antibodies (cANCA) and anti-glomerular basement antibodies (anti-GBM) were found in serum. Renal biopsy revealed extracapillary glomerulonephritis with diffuse half-moon formations. Immunohistology showed a diffuse granular pattern for immunoglobulin G, M and complement C3, without linear deposits. Immunosuppressive treatment combined with plasmapheresis brought about rapid clinical improvement and normalization of the lung involvement and renal function, as well as a fall in the cANCA titre. During a follow-up period of 5 years there has been no recurrence of symptoms, although the anti-GBM titre remained strongly positive and the cANCA titre twice rose to abnormal levels.

Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome.

Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early.

Surgical treatment of bilateral chylothorax due to benign lymphangioma of the thoracic duct.

We present a female patient in whom after an 8-year history of recurrent bilateral pleural effusions, a benign lymphangioma of the thoracic duct was diagnosed and successfully treated by ligation of the duct, resection of the tumour and simultaneous decortication of the right pleural space and lung. This observation supports surgical intervention in this condition even in patients of advanced age.

Prolonged survival following palliative renal tumor embolization by capillary occlusion.

Nine patients with renal cell carcinoma and severe hematuria were palliatively treated with a new type of angioocclusion: the concept of capillary embolization. The so-called occlusion gel Ethibloc was used as embolizing agent. Each patient was followed up until death or for at least 4 years. All patients had a stage T3 or T4 tumor, 3 patients had metastases to multiple organs, 3 had lung metastases, and 3 were free of metastatic disease. In all cases, very high volumes (14-40 ml) of the embolizing agent were necessary to achieve total occlusion of the entire arterial compartment. Patients without metastatic disease had a mean survival time of 6 years and 4 months, all of them without signs of malignant disease. Patients with metastases had a mean survival time of 3 years. Compared with the natural history of renal cell carcinoma treated otherwise, this represents a substantial prolongation of survival time. Contrary to other angioocclusive treatment modalities, the concept of capillary occlusion with Ethibloc seems to achieve total tumor destruction.

[Macromolecular basis of filtration and immune complex pathogenesis in the glomerulus]. / Makromolekulare Grundlagen der Filtration und der Immunkomplex-Pathogenese im Glomerulus.

Fractional clearance and ultrastructural studies produce results consistent with the idea that the glomerular filtration barrier is a heteroporous membrane. The majority of the pores being small, excluding molecules like serum albumin and larger moieties, while a low number of pores allow the passage of molecules as big as dimeric ferritin, in very restricted quantities. Cationic macromolecules, of a size which should effectively exclude them from the filtration process, readily gain access to all three layers of the GBM. Depending on charge (pI) and size they can in fact exhibit significant affinity for negatively charged structures in both laminae rarae. In addition, polycations can mediate the glomerular deposition of anionic macromolecules, for example DNA-fragments, by diminishing charge repulsion. A prerequisite for the local formation of glomerular immune complexes is that at least one of the reaction partners has an affinity for the GBM. Antigens bound to structures in the laminae rarae are accessible for circulating antibody. Immune complexes formed with cationic antigen in the lamina rara interna are transferred to the subepithelial region with time. Antigen and antibody molecules can penetrate the lamina densa only in dissociated form. The persistence of glomerular immune complexes can be explained by antigen-antibody lattice formation within the network of proteoglycan chains, followed by covalent binding between components of the complex and structures of the GBM.

[Terminal renal failure caused by interstitial nephritis following mushroom poisoning by Cortinarius speciocissimus]. / Terminale Niereninsuffizienz durch interstitielle Nephritis nach Pilzvergiftung durch Cortinarius speciocissimus.

A 14 year old boy was admitted for vomiting, anorexia, flank pain and leukocyturia/hematuria. Shortly after admission, he developed anuria and acute renal failure so that hemodialysis had to be started. Pre- and post-renal causes were excluded. There were no signs of acute glomerulonephritis; liver enzymes were normal. The 123Iodine-Hippuran scan showed a shock kidney pattern lacking tubular clearance. Renal biopsy revealed an interstitial nephritis with edema and a mixed cellular infiltration. History was empty for nephrotoxic agents except for mushroom ingestion: Five days before admission the boy ate Cortinarius speciocissimus mushrooms, the toxine of which is known to be nephrotoxic, causing irreversible renal failure in severe cases (Orellanus Syndrome). Renal function did not improve much and renal transplantation was performed after 14 months on hemodialysis. In interstitial nephritis of unknown etiology the possibility of mushroom poisoning should be considered.

Size restriction in the glomerular capillary wall: importance of lamina densa.

Cationized monomeric, dimeric and oligomeric ferritins (pI maxima 9.3 to 9.6) were used to study size restriction in the rat glomerular capillary wall. Monomer and dimer ferritins were able to penetrate the lamina densa; trimer and larger aggregates could not, even though they were able to enter the lamina rara interna. This demonstrates that the lamina densa is a size restrictive barrier, cationic molecules with a Stokes-Einstein radius exceeding a value between 6 to 12 nm are excluded. Monomeric and dimeric cationic ferritins were handled differently in the lamina rara externa; monomer accumulated perferentially immediately below the slit membrane whereas dimer was found within the inner regions of the rara externa, nearer to the lamina densa.

[Hemolytic uremic syndrome following juvenile lupus erythematodes disseminatus]. / Hämolytisch-urämisches Syndrom im Gefolge eines kindlichen Lupus erythematodes disseminatus.

A 12.5 year old girl was admitted to hospital with the typical signs of hemolytic uremic syndrome, and systemic lupus erythematodes as well. On the basis of clinical, blood chemistry, and histological findings we assumed an hemolysis-induced form of hemolytic-uremic syndrome as the most likely pathogenic mechanism. The child also suffered from congenital IgA-deficiency and produced an inhibitor against coagulation factor VIII. Congenital IgA-deficiency, systemic lupus erythematodes, inhibitor-induced hemophilia and hemolytic uremic syndrome are suggested to form a pathogenic sequence.

Reduced content and abnormal distribution of anionic sites (acid proteoglycans) in the diabetic glomerular basement membrane.

Sulfated proteoglycans (fixed anionic sites) on the glomerular basement membrane (GBM) of kidneys from diabetic and nondiabetic patients have been demonstrated by electron microscopy using polycationic dyes (ruthenium red, polyethyleneimine). These substances were used for immersion fixation of renal biopsy specimens. The thickened GBM of diabetics revealed a reduced proteoglycan content within both the narrowed laminae rarae, where normally particles were seen at 60 nm intervals. Proteinuria was observed in all such cases, but no immunopathological alterations of the basement membranes were seen. With both tracer substances anionic sites were also demonstrated in different segments of the thickened lamina densa in diabetics. In polyethyleneimine-treated biopsies some segments of the membrane showed increased anionic moieties at the junction of the basement membrane and the epithelial and endothelial cell membranes. These are probably acid glycoproteins linked to the cell membrane and the synthesis of these basement membrane components may represent a compensatory mechanism seeking to restore normal permeability.

[Kidney tumor embolization. Progress, experiences and complications]. / Nierentumorembolisation. Fortschritte, Erfahrungen und Komplikationen.

Indications for preoperative and palliative embolization of renal tumors have been restricted due to the failures caused by insufficient tumor blockage. Personal experiences using a variety of materials (balloon n = 18, gelfoam n = 10, ethibloc1 /glucose n = 23) and their effectiveness are presented. special emphasis is placed on the influence of parasitic collaterals and the complication rate on the various procedures. Clinical results corroborate those obtained from our own animal experiments: only a capillary embolization that is based on the tumor volume exhausts the current possibilities of therapeutic vascular occlusion of tumors.

Synthetic amino-acid diet prolongs survival in autoimmune murine disease.

The effect of substituting a fully synthetic diet for standard laboratory pellet feed on the course of spontaneous autoimmune disease in New Zealand Black/White hybrid mice was examined. Delays in the development of anti-nuclear antibody, proteinuria and circulating immune complexes were seen; the survival was markedly prolonged. This type of dietary manipulation has a beneficial effect on the course of murine autoimmune disease.

[Experimental conditions for embolization treatment of renal hypertension]. / Experimentelle Voraussetzungen für die Embolisationsbehandlung der renalen Hypertonie.

An experimental study was carried out on 146 rats with hypertension in order to determine whether the intensive collateral circulation which develops in reno-vascular hypertension is responsible for the high failure rate following clinical embolisation. Ethibloc embolisation, which fills the capillaries, is as effective as nephrectomy, whereas ligature of the renal artery fails to affect the hypertension.

Interaction of cationized antigen with rat glomerular basement membrane: in situ immune complex formation.

The influence of charge and size on antigen binding to the rat glomerular basement membrane (GBM) was investigated. Chemically cationized ovalbumin, human serum albumin (HSA), human immunoglobulin G (Hu IgG), horse spleen ferritin and human immunoglobulin M (Hu IgM) were injected into rats intravenously. By immunofluorescence significant glomerular binding occurred when the pI exceeded a threshold value of 8.5 to 9.5. At a given pI antigen binding increased with molecular size. Cationized Hu IgM bound only weakly to the glomerular capillary wall, presumably excluded due to size. Subepithelial immune deposits were formed only when antibody was injected subsequently. Detailed electron microscopic studies on in situ formation of immune complexes were performed using cationized horse spleen ferritin. Early on subendothelial deposits were very marked, giving way to subepithelial deposits with time. Under the conditions employed, it appears that deposits can be formed directly at the subepithelial locus but that complexes are also formed subendothelially, dissociating into free molecules or small complexes and then migrating through the lamina densa and reforming.

Capillary embolization with Ethibloc: new embolization concept tested in dog kidneys.

Collateral vessels in tumors and arteriovenous malformations limit the effectiveness of therapeutic embolization. Capillary propagation of embolization media represents a possible solution of the problem. Embolization with Ethibloc (Hamburg-Norderstedt), a vegetable protein dissolved in alcohol, was performed in 15 renal arteries of dogs. Three embolized kidneys were completely resorbed, and four kidneys showed complete necrosis microscopically. Ethibloc in combination with 40% glucose guarantees homogenous embolization of the entire arterial bed including the capillaries. No complications were observed in other organs.

[Capillary embolization. Part II. Occlusion of the entire arterial system of experimentally induced renal tumors ]. / Kapilläre Embolisation. Teil 2: Verschluss des gesamten arteriellen Gefässsystems experimentell erzeugter Nierentumoren.

221 renal rat tumors (induced by Dimethylnitrosamine) are embolized by gelfoam powder, IBC/Lipiodol and Ethibloc/Glucose. The effect of those embolization media is compared to ligation and glucose perfusion. Recurrencies and rate of surviving tumor tissue are dependent on the stage of the neoplasm, sufficient capillary propagation of the medium, and exact volume-dependent embolization. It could be proven that large areas of renal rat tumors are equally supplied by the main artery and parasitary collaterals. Only homogeneous distribution and complete downstream propagation of the embolization medium from the main artery to the capillaries will achieve breakdown of this parasitary supply. Glucose governed Ethibloc embolization achieves in 80% of tumors with a 6 fold renal volume and in 50% of larger tumors complete necrosis. It has the lowest complication rate of all tested materials.

[Capillary embolization. Part I: occlusion of the entire arterial system of the rat kidney (author's transl)]. / Kapilläre Embolisation Teil I: Verschluss des gesamten arteriellen Gefässsystems der gesunden Rattenniere.

Effect of tumor embolization is limited by parasitary blood supply. The influence of those collaterals should be decreased by transporting the embolization medium into the capillaries and tumor sinusoids. Controlled and safe capillary embolization is developed from studies of obtainable radiodensity, viscosity, and occlusion mechanism of Gelfoam-powder, IBC, and Ethibloc. The efficiency of these substances is compared to simple arterial ligation in experimental series with 400 Wistar rats. It is shown that ligation is comparable to insufficient capillary transport of the medium leaving islands of microscopically intact parenchyma. Easy application and total necrosis is guaranteed only by Ethibloc. Success of embolization is strictly volume dependent. Preinjected glucose is mandatory for homogenous distribution and peripheral transport.