The critical role of innate immunity in kidney transplantation

For a long time now, kidney transplant rejection has been considered the consequence of either cellular or antibody-mediated reaction as a part of adaptive immunity response. The role of innate immunity, on the other hand, had been unclear for many years and was thought to be only ancillary. There is now consistent evidence that innate immune response is a condition necessary to activate the machinery of rejection. In this setting, the communication between antigen-presenting cells and T lymphocytes is of major importance. Indeed, T cells are unable to cause rejection if innate immunity is not activated. This field is currently being explored and several experiments in animal models have proved that blocking innate immunity activation can promote tolerance of the graft instead of rejection. The aim of this review is to systematically describe all the steps of innate immunity response in kidney transplant rejection, from antigen recognition to T-cells activation, with a focus on clinical consequences and possible future perspectives

Complicazioni Scheletriche Dopo Trapianto Renale

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Erdheim-Chester disease : from palliative care to targeted treatment

Erdheim-Chester disease (ECD) is a life-threatening multi-systemic non-Langerhans histiocytosis with cardiovascular complications as the leading cause of death. ECD affects the kidneys in up to 30% of cases, with fibrotic tissue deposition in the perirenal fat and renal hilum. Diagnosis is usually based on histological analysis of the pathologic tissue, which typically shows xanthogranulomatous infiltrates of foamy CD68+/CD1a-histiocytes surrounded by fibrosis. A consistent percentage of patients affected by ECD develop renal failure and hypertension as a consequence of renal artery stenosis and hydronephrosis. These conditions have been generally treated with the placement of stents and nephrostomies that frequently led to disappointing outcomes. Before the introduction of interferon-alpha (IFN\u3b1) treatment, the mortality rate was as high as 57% in the long term. Recent studies have granted new insights into the pathogenesis of ECD, which seems to bear a dual component of clonal and inflammatory disease. These advances led to use specific therapies targeting either the oncogenes (BRAFV600E) or the effectors of the immune response implicated in ECD (IL-1, TNF\u3b1). Drugs such as anakinra (recombinant human IL-1 receptor antagonist), infliximab (monoclonal antibody against TNF\u3b1) and vemurafenib (inhibitor of mutant BRAF) showed promising results in small single-centre series. Although larger trials will be needed to address the impact of these drugs on ECD prognosis and to select the most effective treatment, targeted therapies hold the premises to drastically change the outcome of this condition. \ua9 2014 The Author

Posttransplantation malignancy in a patient presenting with weight loss and changed bowel habits: a case report

BACKROUND: Advancements in immunosuppressive therapy have significantly improved patient and graft survival following renal transplantation. This is paralleled by an increasing occurrence of posttransplantation malignancy. CASE PRESENTATION: We report on a patient who presented with a history reminding of colon cancer seven years after receiving a kidney transplant. Initial diagnostic imaging seemed to confirm this diagnosis showing a constricting colonic lesion. To our surprise, colonoscopy findings were unremarkable. Review of the imaging studies revealed that the tumor-like picture was caused by the renal graft impressing the intestine. The following search for malignancy in other locations resulted in the diagnosis of glioblastoma multiforme of which the patient died several weeks later. CONCLUSION: Follow-up of renal transplant patients must include screening tests directed at tumor detection. Imaging studies and other tests in this patient group should be interpreted by physicians who are familiar with transplant related peculiarities

Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction

Seven patients with acute renal failure due to gross haematuria caused by glomerulonephritis are described. Gross haematuria lasting 4-40 days led to acute impairment of renal function of variable severity (peak plasma creatinine 1.3-12 mg/dl) and duration. While partial recovery of renal function occurred in all patients within few days, complete remission was observed only some months later. Three patients had IgA nephropathy (2 the primary form and 1 nephritis secondary to Schönlein-Henoch purpura), two patients had acute postinfectious glomerulonephritis, andtwo others had focal necrotizing (pauci-immune) glomerulonephritis. The glomerular changes seen in renal biopsy were not enough to explain per se the renal function impairment. Tubular changes, however, were severe and consisted of tubular necrosis, erythrocyte casts, erythrocyte phagocytosis by tubular cells, accompanied by interstitial damage (oedema, red-cell extravasation, and inflammatory infiltrates). Study of the renal biopsies by immunofluorescence revealed retrodiffusion of Tamm-Horsfall protein into the glomerular Bowman's space, a sign of obstructed tubular flow in any case. It is concluded that acute renal failure due to gross haematuria in glomerulonephritic patients may not occur only in IgA nephropathy, as reported so far, and is not associated with intratubular obstructio

Ureteral endometriosis: a rare and underdiagnosed cause of kidney dysfunction

Little attention has been paid by the renal literature to ureteral endometriosis, a rare and silent disorder that can eventually lead to renal failure. In endometriosis, the ureteral involvement can be limited to a single ureter, more often the left one, or both ureters with consequent urine tract obstruction and ureterohydronephrosis. In most cases, the ureteral obstruction is caused by endometrial tissue surrounding the ureter (extrinsic ureteral endometriosis). In the remaining cases, endometrial cells are located within the ureter (intrinsic ureteral endometriosis). Progressive ureteral obstruction can be insidious in onset and can ultimately lead to renal failure if a correct diagnosis is missed. The true incidence of renal failure caused by endometriosis is completely unknown, although cases have been reported in the literature. The diagnosis of ureteral endometriosis is difficult since the disease may be clinically silent or associated with non-specific symptoms. Only a high index of suspicion and radiological support may help to obtain an early diagnosis. However, while renal imaging is useful in the cases of extrinsic endometriosis, the diagnosis of intrinsic endometriosis often requires ureteroscopy or laparoscopy. The prognosis of ureteral endometriosis depends on the time of diagnosis. In too many cases of bilateral obstruction, the patient is referred to the nephrologist because of an advanced, irreversible renal failure. Although some patients may benefit from progestin or anti-arotamase therapy, in most cases of ureteral endometriosis surgery is needed, laparoscopy surgery being preferred today to laparatomy

Should we really STOP treating patients with IgA nephropathy with steroids?

IgA nephropathy (IgAN) is the most common primary glomerulonephritis all over the world. Once considered as a benign disease, today the scientific community is aware that a significant percentage of patients eventually progress to end-stage kidney disease (ESKD). The rate of progression is often very slow. Since 1980s, several therapeutic attempts have been made with steroids. Despite different molecules, doses, and lengths of treatment, the majority of uncontrolled and controlled studies found benefits in terms of proteinuria reduction and reduction of the risk of ESKD. This was obtained with reasonable safety and tolerability, especially when steroids are given at relatively low dose and for a period not exceeding 6 months. Recently, two randomized controlled trials have questioned the efficacy and safety of steroid therapy in IgAN. However, these trials have many drawbacks that are to be considered when interpreting the findings

Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome

<p>Abstract</p> <p>Background</p> <p>Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.</p> <p>Methods</p> <p>A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988–2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFR_e), histopathology, type and duration of treatment, and clinical status at final evaluation.</p> <p>Results</p> <p>13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 ± 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 ± 2.5 and all patients had a normal GFR_e. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications – prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 ± 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 ± 3.1. The mean GFR_ewas 127 ± 57 mL/min/m². Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.</p> <p>Conclusion</p> <p>IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.</p