Post Renal Transplant Malignancies; A Basic Concept.

BACKGROUND: Kidney transplantation remains the best possible solution for patients with chronic kidney disease, providing better long-term outcomes and drastically improving quality of life. However, it comes with its own set of risks. The use of immunosuppressives following renal transplants has been shown to increase the development of malignancies and infections, and the occurrence of post-transplant malignancies is now the third most common cause of death in transplant patients. This involves multiple mechanisms, including the carcinogenic tendency of some immunosuppressive drugs, along with the induction and promotion of post-transplant malignancies by certain viruses. The quantification of Cancer risk must be made an integral part of the overall management of transplant patients, and appropriate follow-up screening needs to be adopted. Kaposi's sarcoma, lymphoma, and non-melanoma skin cancers have a greater incidence. If a malignancy develops immediately after transplantation, it may have been transmitted from the donor; donor-transmitted and donor-derived tumours may be differentiated based on a two-year time limit. Immunosuppressive medications with carcinogenic tendencies, reduced immunological control of oncogenic viruses, and poor immunosurveillance remain the most important risk factors. The gravity of this situation is further exacerbated by the fact that not only is there an increased risk of developing these malignancies in the post-transplant period, but the prognosis is also worsened when compared to non-transplant patients. All transplant centers should therefore adopt a multidisciplinary approach including early detection and prompt treatment, to improve outcomes in transplanted patients.

The Beneficial Role Of Anti-Phospholipase A2 Receptor Auto-Antibodies And Rituximab In The Management Of Recurrent Primary Membranous Nephropathy After Kidney Transplantation.

BACKGROUND: Recurrence of the primary kidney disease causing graft loss in an otherwise good functioning graft in post renal transplantation period is a well-known entity. Approximately 15% of the graft failure occurs secondary to recurrence of the primary glomerulonephritis in post renal transplant period. Regarding primary glomerulonephritis, almost 33-35% of patients suffering from primary membranous nephropathy (PMN), an organ specific auto-immune podocytopathy reach end stage renal disease (ESRD) and renal transplant is then the only treatment modality of choice for them. But, unfortunately 30-50% will experience the disease recurrence and 40-50% will end up with graft loss. The discovery of M-type anti phospholipase auto antibodies (APLA2R-ab) has changed the paradigm. Different remarkable studies are available in the literature that have concluded that APLA2R-ab titers if performed before the renal transplantation are helpful in predicting the disease recurrence and their titration in post-renal transplant period is clinically relevant to see the risk of disease recurrence and its progression, help in treatment monitoring and also to observe the treatment response in terms of complete or partial remission of the disease. Till now, there are no evidence-based guidelines available for the prevention of rPMN in post renal transplant period. The traditional treatment regimens beneficial for the management of PMN in native kidneys are associated with certain serious side effects in post renal transplant period. Rituximab, an anti-CD20 monoclonal antibody (anti CD20 mAb) has emerged as a promising treatment option for such patients. CONCLUSIONS: In conclusion an approach intending an early diagnosis of the rPMN by using the APLA2r levels in serum and its management by utilizing rituximab has proved worthy in minimizing the risk of allograft loss secondary to recurrence of PMN in post renal transplant period. However further studies are still awaited regarding the efficacy, dose and duration of the treatment.

Contrast Induced Nephropathy In High Risk Patients - Myth Or Reality.

BACKGROUND: Contrast induced nephropathy (CIN) is a potential stumbling block in administration of contrast media. CIN has been defined as an elevation of serum creatinine (sCr) of more than ≥0.5 mg/dl (44 µmol/l) or 25% from the baseline within 48-72 hours in the truancy of alternate tenets of acute kidney injury. Incidence of CI-AKI in patients undergoing coronary angiography with normal baseline renal function was reported to be <3%. However, the occurrence of CI-AKI was found to be as high as 50% in CKD patients undergoing Coronary Angiography. This high incidence reported by different studies is mainly because of the difference in definition, underlying renal failure, type and dose of contrast media used and frequency of other co-existing important causes of acute kidney injury (AKI). Recent studies have been published showing that risk of CIN is an overestimated and over-reckoned entity in literature. Objective: To determine the frequency of CIN in CKD patients with Creatinine clearance (Crcl) less than 60 ml/min undergoing contrast exposure. METHODS: We conducted Prospective, controlled single center trial in 42 patients having the creatinine clearance of less than 60 ml/min, they were risk stratified according to Mehran scoring system and underwent coronary angiography or contrast enhanced CT scan with contrast and specific protocol for prevention of CIN including intra-venous (IV) hydration with 0.9% Normal Saline was given before the procedure and were followed up to initial 72 hours post procedure. RESULTS: 33 out of 42 patients, i.e., got adequate hydration as per protocol however 11 patients underwent procedure as pre-existing condition did not allow so. Out of 42 patients, risk stratification according to Mehran Scoring system revealed that 15 patients out of 42 patients were included in very high risk group, 14 were in high risk group and 13 patients were in intermediate risk group. Our experience revealed that 5 out of 42 patients (11.3%) were those who experienced CI-AKI and interestingly none of them required haemodialysis. CONCLUSIONS: Our study has raised serious question on incidence of CIN in high risk patients as reported previously. However, more studies are needed over this issue till that time we might consider CIN A myth rather than a reality.

Rituximab In The Treatment Of Refractory Idiopathic Membranous Nephropathy In Pakistani Population.

This is the time of paradigm shift in the treatment of primary membranous nephropathy which carries a major position in causing nephrotic syndrome in adult population and has been labelled as a cause of idiopathic primary glomerulonephropathy in about 90% of patients. It is two folds more common in male population as compared to female population. It is held responsible for about 0.7% cases of end stage kidney disease. However, unfortunately, the optimal treatment for idiopathic membranous nephropathy is still unresolved. Rituximab has been made especially to attach to CD20 receptors and therefore cause depletion of B cells. It has been found to be a potential treatment option for idiopathic membranous nephropathy. We present four cases of primary idiopathic membranous nephropathy that were successfully treated with rituximab. They were all previously treated with conservative management followed by immunosuppression therapies but none of them was fortunate enough to achieve partial or complete remission. Therefore, all of them were given two doses of rituximab (375 mg/m2), two weeks apart. Except for only one of the patients who required a second round of rituximab therapy, they all achieved complete remission of the disease without any significant side effects of the drug. This represents that those patients of idiopathic membranous nephropathy who are refractory cases with use of steroids, calcineurin inhibitors, (cyclosporine or tacrolimus) or alkylating agents (cyclophosphamide or chlorambucil) still have a hope in the form of Rituximab which has no doubt shown promising results in Pakistani population. Indeed, Rituximab may also be used early in the course of the disease to improve the outcome of the disease.

Immune thrombocytopenic purpura presenting in a patient after renal transplant for diabetic nephropathy.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is primarily characterized by immune-mediated destruction of platelets in circulation. Major treatment options range from careful observation, steroids, immunosuppressive medications, immunoglobulins to splenectomy. Interestingly and rarely, ITP has also been reported after solid organ transplantation in patients receiving immunosuppressive medications. While the incidence of new onset ITP after solid organ transplant is comparatively well documented, new onset ITP after renal transplant has only been reported in two patients. Both these patients underwent renal transplant for underlying Immunoglobulin-A (IgA) nephropathy and were treated effectively with steroids. We present successful management of the first reported case of new-onset ITP presenting after renal transplant in a patient with underlying diabetic nephropathy. The case report discusses the potential management strategies in such a novel scenario aiming simultaneously for a well-functioning renal graft, adequate hemostasis, minimum therapy- related morbidity and least cost implications for the patient. CASE PRESENTATION: A 43-year-old male with hypertension and diabetes mellitus (DM), complicated by nephropathy and retinopathy, underwent pre-emptive living related renal transplant by donation from his 33-year-old wife. His immediate post-transplant period was unremarkable. Six months after the transplant, he presented with isolated thrombocytopenia. An extensive workup revealed no clinical or laboratory evidence of unusual substance intake, infection, hemolysis, microangiopathy, autoimmune disease or hematological malignancy. Eight months after the transplant, while the patient was maintained on steroids, cellcept and tacrolimus, his platelet count dipped to 13,000/microL and he had an episode of mild epistaxis. He was administered steroids in line with the adult ITP management protocol. Steroids were well tolerated, and platelet counts showed a good response to therapy. Steroids were then successfully tapered over the next ten weeks with steady and acceptable platelet counts and graft function. CONCLUSIONS: The case report discusses the diagnostic considerations and successful management of new-onset post-renal transplant ITP. It also highlights the various therapeutic options available in the medical armamentarium including shuffling of immunosuppressive drugs, rituximab, thrombopoietin receptor agonists (TPO's) and splenectomy for their potential use in complicated scenarios like relapsing, or steroid-refractory post renal transplant ITP.

Osmotic nephrosis with mannitol: review article.

Mannitol is commonly used to lower intracranial and intraocular pressures. Large doses/massive infusions of mannitol have been found to be associated with acute renal failure (MI-ARF), that is, osmotic nephrosis. While many researchers have reported individual experiences with this pathology, we felt that there is need of an updated comprehensive review of all reported cases with elaboration of etiology, pathogenesis, diagnosis and management plan for MI-ARF. The purpose of the present communication is to share our own experience with MI-ARF, to review the effect of mannitol on kidney function and to highlight the dynamics of MI-ARF with considerations for the cautious use of mannitol in patients with risk factors for kidney diseases.

Cyclosporine versus tacrolimus maintenance therapy in renal transplant.

OBJECTIVES: Several studies have shown comparable results in long-term graft and patient survival, comparing a tacrolimus-based therapy to cyclosporine, while other studies have shown that a tacrolimus-based regimen had a better renal function with fewer episodes of acute rejection. Most of these studies were in a white population. We describe our experiences comparing tacrolimus versus cyclosporine maintenance therapy in a Saudi population. MATERIALS AND METHODS: All patients from 2003 until 2008 in our transplant clinic were evaluated. A retrospective analysis was done comparing patient and graft survival, kidney function, and metabolic profile. RESULTS: There was no statistical difference in acute rejection rate between the cyclosporine group and the tacrolimus group (18.7% vs 20.9%; P = .756). Mean serum creatinine was not statistically different between the 2 groups. Patient and graft survival at 1 and 2 years also were similar. Although patient and graft survival were similar, the cyclosporine group had a higher level of cholesterol compared with the tacrolimus group (4.6 ± 1.03 mmol/L vs 4.1 ± 0.80 mmol/L; P = .010). CONCLUSIONS: There is no difference in 1- or 2-year patient and graft survival between patients maintained on cyclosporine compared with tacrolimus. However, patients on cyclosporine had a higher blood pressure and serum cholesterol level.

Reversible posterior leukoencephalopathy syndrome in a patient of FSGS with heavy proteinuria.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a neurological syndrome characterized by headache, seizures, and visual loss, often associated with an abrupt increase in blood pressure. It was first described by Hinchey and colleagues in 1996 when they described a case series. RPLS has been described in number of medical conditions, renal dysfunction being one of them. Prompt diagnosis and therapy with antihypertensives, anticonvulsants, removal of any offending medication, and treatment of associated disorder are essential because early treatment might prevent progression to irreversible brain damage. Here, we report a case of young man with focal segmental glomerulosclerosis (FSGS) and heavy proteinuria, who developed classical, clinical, and neurological features of RPLS with complete recovery.

Transplant tourism outcome: a single center experience.

BACKGROUND: Transplant tourism is the term used for patients who travel abroad for transplantation. Transplant tourism has always been surrounded with controversy regarding how these organs were obtained, the donor's care after transplantation, and the recipient outcome. Many authors have found that the outcome of the recipients in transplant tourism is inferior to those transplanted in their own countries. However, most these studies were small, with the latest one including only 33 patients. Here, we describe the outcome of 93 patients who were transplanted abroad compared with local transplantation. MATERIAL AND METHODS: All transplant patients who were followed up at our Nephrology Clinic from 1998 until 2008 were identified using our data base system. We selected patients transplanted from 2003 and forward because the computerized system for laboratory and electronic records began operation that year. RESULTS: A total of 165 patients were identified (93 in the tourist group and 72 in the local one). Transplant tourists had a higher rate of acute rejection in the first year compared with local transplantation (27.9% vs. 9.9, P=0.005), higher mean creatinine at 6 months and 1 year (120 vs. 101 micromol/L, P=0.0007, 113 vs. 98 micromol/L, P=0.008). There was no statistical difference in graft or patient survival in 1 or 2 years after transplantation. However, transplant tourist had a higher rate of cytomegalovirus infection (15.1% vs. 5.6%, P=0.05) and hepatitis C seroconversion (7.5% vs. 0%, P=0.02). CONCLUSION: Transplant tourists had a more complex posttransplantation course with higher incidence of acute rejection and infectious complications.

Regression of brown tumor of the maxilla in a patient with secondary hyperparathyroidism after a parathyroidectomy.

Brown tumors or osteoclastomas are erosive bony lesions arising as a complication of hyperparathyroidism. In patients with end-stage renal disease, brown tumors are uncommon skeletal manifestations that are usually seen in severe forms of secondary hyperparathyroidism. Initial treatment involves the correction of hyperparathyroidism, which usually leads to regression of the tumors. We report a case of brown tumors of the maxilla in a 24-year-old female referred to us by a local hospital, where she had been on regular hemodialysis for >10 years. After a complete biochemical and radiological workup, she underwent a total parathyroidectomy, which subsequently resulted in significant regression of her tumor.

Catheter related infection in hemodialysis patients.

To determine the frequency of hemodialysis (HD) catheter related infection, causative microorganisms and predisposing factors contributing to these infections at our center, we conducted a prospective study in 2007 involving 57 (45.6% males) patients in whom a temporary catheter was inserted for HD. The patients were followed for one month to document any episodes of hemodialysis catheter related infection (HCRI). There were 11 (19.3%) patients who developed HCRI proven by blood culture; 5 patients were infected with more than one organism. Staphylococcus Coagulase negative and Staphylococcus aureus (S. aureus) remain the most common pathogens. All the organisms were sensitive to antibiotics administered empirically, however, 3 patients developed multiple resistant S. aureus (MRSA). All the infected patients experienced previous episodes of HCRI, which formed a risk factor in addition to low albumin when compared to the non-infected group (P=0.024 and P= 0.001, respectively). We conclude that the rate of HCRI and the causative organisms found in our study is comparable to previous reports. We still need to adopt measures to minimize the use of temporary vascular accesses by creation of fistulas in a timely fashion.

Gas-forming urinary tract infection.

Emphysematous or gas-forming infections, a very small percentage of bacterial infections of the urinary tract, attract importance because of their life threatening potential. Herein, we report a 60-year-old Saudi female patient who was a known case of Diabetes mellitus for 15 years. She was admitted with left flank pain of 5 days duration, abdominal distension, nausea, vomiting and chills associated with increased frequency of urine, urgency, and dysuria. She had leukocytosis, high blood sugar, elevated urea and creatinine and pyuria. Urine culture grew Escherichia coli. Ultrasound and CT scan showed left pelvicalyceal dilatation and air in the left kidney and urinary bladder. She was treated with a prolonged parenteral antibiotic course, and insulin, with complete recovery.

Novel CuI/tributyl phosphine catalyst system for amination of aryl chlorides.

A simple and efficient methodology for the synthesis of triarylamines from aryl chlorides in a single step has been demonstrated using a novel CuI/tributyl phosphine catalyst system with high activity and selectivity (80-87% yield).