Cases reported "Kidney Diseases"

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1/39. Nephrotoxicity attributed to meglumine antimoniate (Glucantime) in the treatment of generalized cutaneous leishmaniasis.

    BACKGROUND: Pentavalent antimonials have became of basic importance for the treatment of leishmaniasis. Their most severe side effects have been reported to be increased hepatic enzyme levels and electrocardiographic abnormalities. Nephrotoxicity has been rarely related. OBSERVATIONS: We report a case of generalized cutaneous leishmaniasis involving a 50-year old male patient who was submitted to treatment with meglumine antimoniate (Glucantime). He developed acute renal failure (ARF) due to acute tubular necrosis (ATN), followed by death after receiving a total of 53 ampoules of Glucantime. CONCLUSIONS: The treatment with Glucantime was responsible by ARF diagnosed in this patient. The previous urine osmolarity and serum creatinine levels were normal and the autopsy showed ATN. It should be pointed out if ARF may also be explained by massive deposits of immunocomplexes by leishmania antibodies and antigens due to the antigenic break by the antimonial compound, since our patient presented countless lesions covering the entire tegument, similar to the Hexheimer phenomenon, but at the autopsy no glomerular alterations were seen.
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2/39. Renal involvement of thrombotic thrombocytopenic purpura: special reference to the glomeruloid structures.

    We report the case of a 9-year-old girl with biopsy-proven renal thrombotic microangiopathy in thrombotic thrombocytopenic purpura (TTP), with particular reference to the glomeruloid structures. The renal biopsy sample from this TTP patient revealed platelet thrombus deposition, a glomeruloid structure and aneurysm with relative sparing of the glomeruli. The glomeruloid structure displayed a proliferation of mainly capillary-sized channels lined by factor viii-related, antigen-positive plump endothelial cells embedded in the edematous connective tissue. These glomeruloid vessels communicated with the aneurysmal segment at the end portion of the arteriolar branch. We believe that the glomeruloid structures in TTP represent not merely organization or recanalization of thrombus but rather active angiogenesis through aneurysmal dilation in the arteriolized vessel, probably initiated by platelet agglutination.
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3/39. Rapidly progressive antineutrophil cytoplasm antibodies associated with pulmonary-renal syndrome in a 10-year-old girl.

    CONTEXT: The term pulmonary-renal syndrome has been used frequently to describe the clinical manifestations of a great number of diseases in which pulmonary hemorrhage and glomerulonephritis coexist. The classic example of this type of vasculitis is Goodpastures syndrome, a term used to describe the association of pulmonary hemorrhage, glomerulonephritis and the presence of circulating antiglomerular basement membrane antibodies (anti-GBM). Among the several types of systemic vasculitides that can present clinical manifestations of the pulmonary-renal syndrome, we focus the discussion on two types more frequently associated with antineutrophil cytoplasm antibodies (ANCA), microscopic polyangiitis and Wegener's granulomatosis, concerning a 10 year old girl with clinical signs and symptoms of pulmonary-renal syndrome, with positive ANCA and rapidly progressive evolution. CASE REPORT: We describe the case of a 10-year-old girl referred to our hospital for evaluation of profound anemia detected in a primary health center. Five days before entry she had experienced malaise, pallor and began to cough up blood-tinged sputum that was at first attributed to dental bleeding. She was admitted to the infirmary with hemoglobin = 4 mg/dL, hematocrit = 14 %, platelets = 260,000, white blood cells = 8300, 74 % segmented, 4 % eosinophils, 19 % lymphocytes and 3 % monocytes. Radiographs of the chest revealed bilateral diffuse interstitial alveolar infiltrates. There was progressive worsening of cough and respiratory distress during the admission day, when she began to cough up large quantities of blood and hematuria was noted. There was rapid and progressive loss of renal function and massive lung hemorrhage. The antineutrophil cytoplasm antibody (ANCA) test with antigen specificity for myeloperoxidase (anti-MPO) was positive and the circulating anti-GBM showed an indeterminate result.
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4/39. Molecular characterization and sequence analysis of polyomavirus BKV-strain in a renal-allograft recipient.

    The significance of polyomavirus (PV) infection was investigated in a 53-year-old patient who underwent renal transplantation and was treated with triple immunosuppressive therapy (tacrolimus, prednisone, and azathioprine). A renal biopsy taken because of the suspicion of acute rejection showed focal inflammatory interstitial infiltration, tubulitis, and tubular cell nuclear changes consistent with the hypothesis of viral infection. Both the tubular and decoy cells identified by means of urinalysis positively stained for anti-SV40 antibody. polymerase chain reaction performed on the dna extracted from renal tissue and isolated from urine showed the presence of an antigenic variant (AS) of the BKV archetype after sequence analysis of the transcription control region (TCR). On the basis of the diagnosis of BKV infection, immunosuppressive therapy was reduced. The patient's renal function improved and was still stable 8 months later when urinalysis showed only a few decoy cells, which were found to be infected by JC but not bk virus. These data suggest that only the BKV, probably favoured by immunosuppressive therapy (tacrolimus), causes renal damage. It is worth underlining that even small and sporadic viral genome mutations may lead to pathologic effects.
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5/39. Successful renal transplant outcome after intravenous gamma-globulin treatment of a highly sensitized pediatric recipient.

    Approximately 10% of patients on the renal transplant (Tx) cadaver waiting list have high (> 20%) panel-reactive antibody (PRA) levels to human leukocyte antigens (HLA). Intravenous gamma-globulin (IVIG) has been shown to reduce anti-HLA cytotoxic antibody levels through an anti-idiotypic antibody-blocking effect. We report a successful renal Tx outcome in a 7-yr-old-girl with high PRA levels owing to a failed renal Tx who experienced a significant reduction in PRA levels (from 96% to 0%) concomitant with IVIG therapy. IVIG was infused weekly (500 mg/kg/week) for 3 consecutive weeks every 12 weeks. Thirty-four months after starting IVIG therapy, the PRA activity dropped to zero and IVIG was stopped. Then IVIG therapy was resumed after 8 months due to a rebound in PRA activity to 52%. Forty-four months after starting IVIG therapy, the patient was cross-matched with a cadaver donor who shared three antigens with the first living donor. The cross-match was positive with the recipient's sera obtained prior to IVIG therapy and negative with the recipient's sera obtained post-IVIG therapy. A successful cadaver renal Tx was performed using anti-thymocyte globulin (ATGAM) induction therapy and a tacrolimus-based immunosuppression protocol. IVIG was given (1 g/kg) prior to Tx and at day 4 post-operatively. A single mild acute rejection episode occurred 10 days post-transplantation that responded to pulse methylprednisolone therapy and an increase in the tacrolimus oral dose. We conclude that a prolonged course of IVIG infusions, without immunosuppressive medications or plasmapheresis, is likely to have been beneficial in modulating the immune response in this highly sensitized recipient. Randomized multicenter trials are required to define the role of IVIG in this specific population.
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6/39. Karyomegalic nephropathy: an uncommon cause of progressive renal failure.

    BACKGROUND: Karyomegalic nephropathy, first identified in 1974, represents an increasingly recognized, but perhaps underdiagnosed condition associated with interstitial nephritis. It undoubtedly leads to end-stage renal disease requiring renal support. methods AND RESULTS: We present a series of six cases of karyomegalic nephropathy. The age at diagnosis was 9-51 years, median 33 years. Impaired renal function, proteinuria, and haematuria were present in the majority of cases. Non-specific elevated liver enzymes were present in three cases. Two patients died soon after transplantation from overwhelming respiratory sepsis. The classical histological features of large, abnormal hyperchromatic nuclei with irregular outlines within epithelial cells were present in renal epithelial cells. Abnormality of dna ploidy distributions compared with age- and sex-matched controls, and characterized by the presence of significant numbers of cells with high ploidy values was present in cases but not in controls. Mitotic figures were absent. Proliferation markers, Ki-67 and proliferating cell nuclear antigen/cyclin were not significantly elevated in those cases examined. Human leukocyte antigen analysis did not support the clustering of A9 or B35, in the cases or their families. CONCLUSIONS: The presence of significant renal impairment, positive urine sediment, abnormal liver enzymes, and early age of onset should alert one to the presence of karyomegalic nephropathy. It represents an underdiagnosed disorder with a high degree of ploidy indicative of karyotypic abnormality.
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7/39. Glomerular vasculopathy after unrelated cord blood transplantation.

    A 1-year-old boy with hemophagocytic lymphohistiocytosis exhibited proteinuria 1 month after unrelated cord blood cell transplantation, which persisted without hematuria. Laboratory study showed an increase of factor viii-related antigen and total plasminogen activator inhibitor, suggesting endothelial injury. Histological examination of autopsy materials showed increased mesangial matrices and double-contoured basement membranes, and ultrastructurally, swelling of the endothelial cells and widening of the subendothelial space with mesangial interposition. thrombosis was not observed at any of the sites. This case may be vasculopathy distinct from thrombotic microangiopathy (TMA) or a variant form of TMA following blood stem cell transplantation (BSCT). This vasculopathy should be considered in the differential diagnosis of proteinuria in the early stages after BSCT.
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8/39. bk virus nephropathy in a patient with ABO-incompatible renal transplantation.

    A 43-year-old woman with end-stage renal disease originating from IgA nephropathy entered chronic haemodialysis therapy. She then received an ABO-incompatible living related renal transplantation. Initial immunosuppression consisted of azathioprine, methylprednisolone and tacrolimus. At 155 days after transplantation, the azathioprine was changed to mycophenolate mofetil for continuous graft dysfunction. Furthermore, a total of three courses of anti-rejection therapy was given. At 665 days after transplantation, diagnosis of BK-virus nephropathy was made by immunohistochemical analysis and viral dna assay. Therefore the immunosuppression therapy was reduced for graft dysfunction. All five renal biopsy specimens were examined retrospectively in order to determine when the bk virus nephropathy had developed. The expressions of SV40 large T antigens were detected from the third (117 days) to the fifth (665 days) biopsies, with increasing numbers of SV40 large T antigen positive cells. In addition, many cells contained inclusion bodies which were already present in the urinary sediment for 3 months post-transplantation. Although it is difficult to make a diagnosis of early stage of BKVN, we have to consider with caution if urinary cells with inclusion body are seen. awareness of BKVN at the earliest opportunity is important in order to avoid over-immunosuppression.
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9/39. The dysregulated glomerular cell growth in denys-drash syndrome.

    While diffuse mesangial sclerosis is traditionally described as being the glomerulopathy of denys-drash syndrome (DDS), the podocyte proliferative lesions may be overlooked in these DDS cases. In the present study, an evolving process is extrapolated from a selected case of DDS that demonstrated glomerulopathy with conspicuous podocyte proliferation. The observation that podocytes express proliferation markers (Ki67, proliferating-cell nuclear antigen and topoisomerase IIalpha) in non-proliferative, mature-looking glomeruli suggests an initial pathogenic act to activate or to keep podocytes from quiescence. The subsequent proliferation of podocytes is in keeping with downregulation of WT1 and cyclin kinase inhibitors of p16 and p21. The emergence of cytokeratin-positive cells in glomeruli that show typical mesangial sclerosis implies elimination of podocytes and replacement with tubular and/or parietal epithelial cells. The final scene of evolving glomerulopathy displays apoptosis and expression of Fas-L and Bax in sclerotic mesangial lesions, which eventually end up with global sclerosis. This novel concept of DDS glomerulopathy implies complex molecular mechanisms involved in glomerular injury.
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10/39. LT, VP1 and TCR-BKV sequence analysis in a patient with post-transplant BKV nephropathy associated with EBV-related PTLD.

    A 10-year-old boy kidney transplant recipient (KTR) developed an abdominal post-transplant lymphoproliferative syndrome (PTLD) followed by bk virus nephropathy (BKVN). bk virus (BKV) and Epstein-Barr virus (EBV) were studied in renal and PTLD tissue by polymerase chain reaction (PCR) assay. Afterwards, the patient was monitored in relation to BKV in urine and serum; transcription control region (TCR)-BK polymorphism sequence analysis was also performed. In the PCR assay, both early large T antigen (LT) and late (VP1) transcriptional BKV coding regions were found in renal tissue, whereas EBV and only LT-BK were detected in PTLD abdominal tissue. On the other hand, TCR sequence analysis revealed the AS genomic BK variant.
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