First case report of using Ofatumumab in kidney transplantation AB0 incompatible. / PRIMO CASE REPORT DI UTILIZZO DELL' OFATUMUMAB NEL TRAPIANTO RENALE AB0 INCOMPATIBILE.

Modern methods for desensitization protocol rely heavily on combined apheresis therapy and Rituximab, a chimeric (murine and human) anti-CD20 antibody used in AB0 incompatible kidney transplants. Severe infusion related reactions due to the administration of Rituximab are reported in 10% of patients. These adverse reactions may hinder the completion of the desensitization protocol. Therefore, it's useful to test alternative B cell depleting therapies. Our clinical case focuses on a 41-year-old male who developed an adverse infusion reaction following the administration of Rituximab and was given Ofatumumab as an alternative treatment. Ofatumumab is a fully humanized monoclonal anti-CD20 antibody. As a fully humanized antibody, Ofatumumab may avoid immunogenic reactions. The patient tolerated the administration of the drug showing no signs of adverse side effects and with good clinical efficacy. Our case report suggest that Ofatumumab is a valid alternative B cell depleting agent.

Evidence of hepatitis E virus transmission by renal graft.

Hepatitis E virus (HEV) can cause chronic infection among immunocompromised patients, especially solid organ transplant recipients, and can evolve to cirrhosis. Several modes of transmission are known. Here we describe the first two cases, to our knowledge, of HEV infection transmitted by a kidney graft from the same infected donor that led to chronic hepatitis. Consequently, systematic screening of donors by HEV serology and HEV RNA detection by polymerase chain reaction, particularly in endemic regions, should be considered.

Evolutive study of children with diffuse mesangial sclerosis.

Diffuse mesangial sclerosis (DMS) is a renal disease that usually presents as a nephrotic syndrome. It is characterized by early onset and rapid progression to end-stage renal disease, and can occur as an isolated finding or as part of the Denys-Drash syndrome. The aim of this study was to characterize clinical features and outcomes of DMS in a cohort of children. We retrospectively analyzed all cases of DMS diagnosed in our hospital between 1973 and 2008 and evaluated the progression of the disease in relation to different variables. We studied 14 patients, four with incomplete Denys-Drash syndrome and one with Frasier syndrome. All patients developed renal failure. Eight patients received a renal transplant with no relapse of the disease. Bilateral nephrectomy was performed in nine patients with end-stage renal disease. Seven patients died, with sepsis being the main cause of death. Diffuse mesangial sclerosis must be suspected in a child that presents with early onset proteinuria and/or rapidly progressive renal failure. Karyotype and WT1 gene analysis should be performed because of the predisposition of patients to develop different types of tumors. This nephropathy has a poor prognosis, but the survival rate has improved in the last decade.

Rapid resolution of EPO-induced pure red cell aplasia after a course of immunoadsorption therapy using protein A columns.

Pure red cell aplasia (PRCA) is a rare, but important, complication of erythropoietin (EPO) replacement therapy in patients with renal disease. There is no consensus about the best way to treat this condition; however, recent reports indicated that immunosuppressive therapy is beneficial. We report a patient with EPO-induced PRCA treated with a regimen initially designed for antifactor VIII antibodies in patients with hemophilia. This regimen consists of immunoadsorption therapy using protein A columns, followed by oral prednisolone and single bolus infusions of intravenous immunoglobulin G and cyclophosphamide. Shortly after the course, a swift and rapid increase in reticulocyte count was evident; the patient became transfusion independent and has remained so during 2 years of follow-up. By means of this report, we wish to encourage others to consider this option when first-line treatments fail.

Increased expression of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor genes in aging human kidney and chronic allograft nephropathy.

BACKGROUND: The goal of the current study was to examine the potential value of p16(INK4a) and p27(Kip1) cyclin-dependent kinase inhibitor (CDKI) genes in the process of human kidney aging in vivo, and in the development of chronic allograft nephropathy (CAN). METHODS: Expression of p16(INK4a) and p27(Kip1) CDKI genes was evaluated and compared in 20 normal human kidney tissues of different ages (range, 21 to 80 years) and in 9 chronically rejected kidney grafts. Age dependency of marker expression was analyzed by the Pearson correlation and linear regression. RESULTS: Expression of p16 in cortical tubular (CTS) and interstitial (CIS) cells of normal kidney was age dependent (correlation coefficients: 0.608 and 0.726, 95% confidence interval [CI]: 0.227 to 0.828 and 0.417 to 0.884, respectively). Cortical tubular expression of p27 was also correlated with increasing age (0.672, 95% CI: 0.327 to 0.859). Linear regression analyses confirmed the linearity of marker relationship with age (coefficient of determination R(2):0.370, 0.452, and 0.527 for CIS p16, CTS p27, and CTS p16, respectively). The mean chronological and predicted graft ages (53 +/- 21 and 76 +/- 8.9 years, respectively) were significantly different (P = 0.0126). The glomeruli, tubules, and interstitial cells of rejected grafts expressed significantly higher levels of p16 and p27 than normal kidneys. Expression of p16 in glomerular and cortical interstitial cells was higher in grade 3 of CAN than in grade 2 (P = 0.013 and 0.004, respectively). CONCLUSION: The results of the current study show that expression of p16(INK4a) and p27(Kip1) CDKI genes is increased in cortical cells of the aging human kidney and in chronic allograft rejection, supporting the senescence theory of CAN.

[Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors]. / Anemia hemolítica por reacción injerto contra huésped en trasplantados renales ABO no idénticos con donantes del grupo sanguíneo O.

Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.

Managing acute myocardial infarction in a renal transplant recipient.

We describe the management of a patient, with a 13-year-old cadaveric renal transplant, who presented with acute myocardial infarction. Successful primary angioplasty was performed to the left anterior descending artery. It was complicated by transient renal failure and pseudoaneurysm of the femoral artery which was managed conservatively.

Surgical management of dialysis-dependent ischemic nephropathy.

PURPOSE: This retrospective review describes surgical management of dialysis-dependent ischemic nephropathy. METHODS: From February 1987 through September 1993, 340 patients underwent operative renal artery (RA) reconstruction at our center. A subgroup of 20 patients (6 women; 14 men; mean age 66 years) dependent on hemodialysis immediately before RA repair form the basis of this report. Glomerular filtration rates (EGFR) were estimated from at least three serum creatinine measurements obtained 26 weeks before and after operation. A linear regression model was used to estimate the mean rate of change of EGFR before and after RA repair. Comparative analysis of kidney status and change in EGFR were performed. The influence of function response on follow-up survival was determined by the product-limit method. RESULTS: Hemodialysis was discontinued in 16 of 20 patients (80%). For these 16 patients, postoperative EGFR ranged from 9.0 to 56.1 ml/min/1.73 m2 (mean 32.4 ml/min/1.73 m2). Two of 16 patients resumed hemodialysis 4 and 6 months after surgery. Discontinuation of dialysis was more likely after bilateral or complete RA repair (15 of 16 patients) versus unilateral repair (one of four patients; p = 0.01). Permanent discontinuation of dialysis was associated with a rapid preoperative rate of decline in EGFR (mean slope log(e) EGFR: -0.1393 +/- 0.0340 without dialysis; -0.0188 +/- 0.0464 with dialysis; p = 0.04, but NS after controlling for multiple comparisons). Immediate increase in EGFR after operation was inversely correlated with the severity of nephrosclerosis (rank correlation: -0.57; 95% confidence interval [-0.83, -0.10]). Follow-up death was associated with dialysis dependence; two deaths occurred among 14 patients not receiving dialysis, whereas five of six patients dependent on dialysis died (p < 0.01). CONCLUSION: Surgical correction of ischemic nephropathy can retrieve renal function in selected patients dependent on dialysis characterized by a rapid decline in preoperative EGFR in combination with global renal ischemia treated by complete or bilateral renal revascularization. After RA repair, discontinuation of dialysis may be associated with improved survival rates when compared with continued dialysis dependence.

Small kidney and hypertension: selection of patients for surgery.

We studied 37 patients with various degrees of hypertension and a small unilateral kidney. Renal vein renin studies were shown to be positive on 19 occasions and negative on 18. Of those positive, 10 had severe and 1 moderate hypertension. Surgery cured 63.3%. In 27% blood pressure improved and 1 patient failed to respond. Eight patients had mild hypertension with a positive renal vein renin ratio (RVRR), but on observation their home blood pressures were normal without medication and they were not considered for surgery. Eighteen patients with mild hypertension and negative RVRR were also not operated. We believe that RVRR is important for a surgical decision, but only in severe and moderate hypertensives. In mild hypertension, measurement of blood pressure at home is normal on most occasions. These are hyperreactive patients and should not have surgery, regardless of the results of their RVRRs.

Original disease of the recipient.

1. The influence that a patient's original disease had on the outcome of kidney transplantation was small when recent transplants (1983 to present) were examined. A difference of only 5% was seen in one-year graft survivals of first cadaver donors. The average one-year survival was 70%; patients with pylonephritis having the best (75%) and SLE patients the worst (65%) survival rates among the major disease categories. 2. There was little difference observed in patient survivals or functional graft survivals in first cadaver transplants among patients with different original diseases. This was also the case with cadaver regrafts; with the exception of polycystic kidney patients who had quite poor graft survival (41% at one year) with regrafts. Pretransplant blood transfusions resulted in increased cadaver graft survival; however the low number of nontransfused patients in many disease categories presented difficulties in examining this effect. 3. The use of cyclosporine resulted in increased cadaver graft survival in all disease categories. One-year cadaver graft survival of cyclosporine-treated patients averaged 75% compared to 63% with noncyclosporine-treated patients. A beneficial effect of cyclosporine use was not consistently seen in transplants involving living-related donors, although perhaps larger numbers of patients are required in order to confirm this observation. 4. Graft survival in diabetic patients was quite good in this analysis of recent transplants. First cadaver one-year graft survival in diabetics was only 4% below the overall average and 2% less with cyclosporine. Patients with both juvenile (75% one-year graft survival) and adult-onset (78% one-year graft survival) forms of the disease had good graft survival when cyclosporine was used for immunosuppression.

Remission of essential hypertension after renal transplantation.

Six patients in whom "essential hypertension" led to nephrosclerosis and kidney failure received kidney transplants from normotensive donors. After an average follow-up of 4.5 years, all were normotensive and had evidence of reversal of hypertensive damage to the heart and retinal vessels. These six patients, all of whom were black, and six control subjects matched for age, sex, and race were admitted to the General Clinical Research Center for 11 days for observation of their blood pressure and their responses to salt deprivation and salt loading. Mean arterial pressure (+/- S.E.M.) among the patients who had previously had essential hypertension was similar to that of the normal controls (92 +/- 1.9 vs. 94 +/- 3.9; P not significant), and both groups had similar responses to salt deprivation and salt loading. Thus, essential hypertension in human beings is shown to be similar to the hypertension seen in spontaneously hypertensive rats in that both can be corrected by transplantation of a kidney from a normotensive donor. This observation supports the concept of the primary of the kidney in causing essential hypertension.

Histologic correlation of transplant rejection diagnosed by computer-assisted sulfur colloid scan.

Sulfur colloid scanning has been suggested as a means of early detection of renal transplant rejection. Visual interpretation of increased uptake by the allograft as opposed to surrounding pelvic structures was taken to signify rejection. In an attempt to increase the accuracy of these scans we programmed a computer to do differential counts between graft and surrounding pelvis and to then calculate a ratio. Hopefully this mathematical determination of increased uptake would be more accurate. These scans were compared with simultaneously obtained biopsy material. Unfortunately, the false negative and false positive rates were too high to make sulfur colloid useful in predicting graft rejection. Finally, our data showed that an early positive scan did not predict long-term outcome as had been suggested by others.

[Indications and contraindications for kidney transplantation]. / Indikationen und Kontraindikationen zur Nierentransplantation.

The indication for renal transplantation has to be made individually in every single case, considering the few absolute contraindications (tumors, acute infections and the presence of cyto-toxical antibodies) and the general risks. Chances of success, resulting from the EDTA-statistics from 1979 concerning the survival rate of patients and the functional rate of the transplant of donors deceased or alive, are discussed as well as possible complications. The good rehabilitation of successfully transplanted patients must be especially emphasized. Risk factors are: advanced age, adipositas, cardio-vascular and pulmonary lesions as well as gastro-intestinal disease in the past and diabetes mellitus with certain reservation. The possible effects the the transplant caused by the underlying disease leading on renal insufficiency and systemic diseases which limit the indication are outlined and discusssed. Good interdisciplinary cooperation in the pre- and postoperative phase is necessary.

[Report on renal transplant patients. Ocular changes due to renal disease and immunosuppressive therapy (author's transl)]. / Bericht über nierentransplantierte Patienten. Augenveränderungen durch Grundleiden und Therapie.

51 patients with renal transplants were examined ophthalmologically 31,1 (1--77) months after the transplantation. 80,4 p. c. showed ocular complications: cataract formation in 43,1 p. c. of the patients examined and increased intraocular pressure values between 22 and 30 mm Hg in 3 patients are to be attributed to the systemic immunosuppressive therapy. Further ocular changes were recurrent subconjunctival haemorrhages due to increased vascular rigidity, calcium phosphate deposits in the conjunctiva due to persistant secondary hyperparathyroidism and fundus changes (pigmentary irregularities in the foveal regions, narrow arterial vessels). Although marked arterial hypertension was observed in 21 patients after the transplantation, no signs of hypertensive retinopathy could be found. Despite the high incidence of ocular complications after renal transplantation the risks of immunosuppressive therapy must be considered as tolerable: cataract formation and increased intraocular pressure do not impair the positive effect of renal transplantation on ocular functions. Regular ophthalmological control examinations of renal transplant patients are advisable.

[Renal transplantation in malignant nephrosclerosis (author's transl)]. / Nierentransplantation bei maligner Nephrosklerose.

Renal transplantation was performed 3 to 64 months after the onset of dialysis in 6 patients with histologically ascertained malignant nephrosclersosis and malignant hypertension, as well as terminal renal failure. Three patients were nephrectomized on both sides before and one after the transplantation. 24 to 105 months after the transplantation all patients were normotensive. Only one patient required low-dosage antihypertensive medication. There was evidence for marked improvement of cardiovascular complications, and no evidence for recurrence of malignant nephrosclerosis in the transplanted kidney.