No metagenomic evidence of tumorigenic viruses in cancers from a selected cohort of immunosuppressed subjects.

The possible existence of yet undiscovered human tumorigenic viruses is still under scrutiny. The development of large-scale sequencing technologies, coupled with bioinformatics techniques for the characterization of metagenomic sequences, have provided an invaluable tool for the detection of unknown, infectious, tumorigenic agents, as demonstrated by several recent studies. However, discoveries of novel viruses possibly associated with tumorigenesis are scarce at best. Here, we apply a rigorous bioinformatics workflow to investigate in depth tumor metagenomes from a small but carefully selected cohort of immunosuppressed patients. While a variegated bacterial microbiome was associated with each tumor, no evidence of the presence of putative oncoviruses was found. These results are consistent with the major findings of several recent papers and suggest that new human tumorigenic viruses are not common even in immunosuppressed populations.

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients.

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9 % of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12 MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.

[Karyomegalic interstitial nephritis: an atypical case]. / La nefrite interstiziale cariomegalica: descrizione di un caso clinico atipico.

Karyomegalic interstitial nephritis (KIN) is a rare disease entity that was first described by Burry in 1974. The prevalence of this disease is less than 1% and its pathogenesis is unclear. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to progressive decline of renal function. The disease has no known treatment. Here, we report on a 50-year-old female patient who presented with asymptomatic progressive decline of renal function. Renal biopsy demonstrated chronic tubulointerstitial nephritis with markedly enlarged and hyperchromic nuclei of tubule epithelial cells the hallmark of karyomegalic nephritis. Clinical and pathologic findings of this case are discussed in light of the available literature.

[Renal biopsy in the lateral position in high risk patients: an opportunity to take advantage of]. / La biopsia renale in decubito laterale nei pazienti complessi: una possibilità da sfruttare.

Percutaneous ultrasound-guided renal biopsy (RB) is the gold standard for diagnosis of renal diseases. The standard procedure involves biopsy in the prone position (PP) for the native kidneys. In high risk patients, transjugular and laparoscopic RB have been proposed. In patients suffering from obesity or respiratory diseases, the RB of the native kidney in the supine anterolateral position (SALP) represents an alternative to these invasive and expensive methods. We illustrate the technique of execution of RB in the lateral position (LP) on native kidneys. The procedure is safe, effective and has reduced the path travelled by the needle biopsy compared with PP and SALP.

[Ultrasound-guided renal biopsy: evaluation of different models of biological simulator]. / La biopsia renale-ecoguidata: valutazione di diversi modelli di simulatore biologico.

Percutaneous ultrasound-guided renal biopsy is the gold standard for diagnosis and treatment of renal diseases. Recently, many studies strongly support the role of renal biopsy for the management of small renal mass. The experience of the operator is crucial in reducing the incidence of major complications. The use of simulators can accelerate the learning curve in those individuals who train in renal biopsy. We describe four simple and affordable phantoms for renal biopsy. The first two simulators were constructed by a porcine kidney wrapped in perirenal fat or covered by a flap of abdominal skin. The third simulator was constructed by embedding a porcine kidney in a turkey breast and olives to simulate the presence of small tumors. For the fourth model, we used the loin of a pork. Given the encouraging results of our in vitro study, we believe that simulators allow trainees to familiarize themselves with the handling of the equipment in an environment that is risk-free when compared to the clinical scenario.

[Goodpasture's disease: a case series]. / La Malattia di Goodpasture: l'esperienza di un singolo centro.

Goodpasture's disease (GD) is an uncommon and severe autoimmune disorder caused by circulating autoantibodies directed against the glomerular basement membrane cross-reacting with the alveolar basement membrane. GD is clinically characterized by rapidly progressive glomerulonephritis, often associated with pulmonary hemorrhage representing a nephrological emergency. We present the clinical features of 9 cases, diagnosed in 1997-2012, in our Renal Unit. Contrary to previous reports, we found a predominance of GD in females and we observed unusual clinical patterns, such as the association with renal vein thrombosis in a pregnant patient, thrombosis of the pulmonary arteries and a late isolated recurrence of alveolitis. In dialysis-dependent patients, renal transplantation can represent an available treatment option.

Lung ultrasound during hemodialysis: the role in the assessment of volume status.

OBJECTIVE: Fluid balance is important in patients undergoing hemodialysis. "Dry" weight is usually estimated clinically, and also, bioimpedance is considered reliable. Ultrasonography of inferior vena cava (IVC) estimates central venous pressure, and lung ultrasound evaluates extravascular (counting B-lines artifact) lung water. Our study was aimed to clarify their usefulness in the assessment of volume status during hemodialysis. METHODS: A total of 71 consecutive patients undergoing hemodialysis underwent lung and IVC ultrasound and bioimpedance spectroscopy immediately before and after dialysis. RESULTS: There was a significant reduction in the number of B-lines (3.13 vs 1.41) and in IVC diameters (end-expiratory diameter 1.71 vs 1.37; end-inspiratory diameter 1.19 vs 0.95) during dialysis. The reduction in B-lines correlated with weight reduction during dialysis (p 0.007); none of the parameters concerning the IVC correlated with fluid removal. At the end of the dialysis session, the total number of B-lines correlated with bioimpedance residual weight (p 0.002). DISCUSSION: The reduction in B-lines correlated with fluid loss due to hemodialysis, despite the small pre-dialysis number, confirming that lung ultrasound can identify even modest variations in extravascular lung water. IVC ultrasound, which reflects the intravascular filling grade, might not be sensitive enough to detect rapid volume decrease. Clinically estimated dry weight had a poor correlation with both bioimpedance and ultrasound techniques. Post-dialysis B-lines number correlates with residual weight assessed with bioimpedance, suggesting a role for ultrasound in managing hemodialysis patients.

Risk of de novo cancers after transplantation: results from a cohort of 7217 kidney transplant recipients, Italy 1997-2009.

To assess incidence and risk factors for de novo cancers (DNCs) after kidney transplant (KT), we carried out a cohort investigation in 15 Italian KT centres. Seven thousand two-hundred seventeen KT recipients (64.2% men), transplanted between 1997 and 2007 and followed-up until 2009, represented the study group. Person years (PY) were computed from 30 days after transplant to cancer diagnosis, death, return to dialysis or to study closure. The number of observed DNCs was compared to that expected in the general population of Italy through standardised incidence ratios (SIR) and 95% confidence intervals (CI). To identify risk factors, incidence rate ratios (IRR) were computed. Three-hundred ninety five DNCs were diagnosed during 39.598PYs, with Kaposi's sarcoma (KS), post-transplant lymphoproliferative disorders (PTLD), particularly non-Hodgkin' lymphoma (NHL), lung, kidney and prostate as the most common types. The overall IR was 9.98/1.000PY, with a 1.7-fold augmented SIR (95% CI: 1.6-1.9). SIRs were particularly elevated for KS (135), lip (9.4), kidney carcinoma (4.9), NHL (4.5) and mesothelioma (4.2). KT recipients born in Southern Italy were at reduced risk of kidney cancer and solid tumors, though at a higher KS risk, than those born in Northern Italy. Use of mTOR inhibitors (mTORi) exerted, for all cancers combined, a 46% significantly reduced risk (95% CI: 0.4-0.7). Our study findings confirmed, in Italy, the increased risks for cancer following KT, and they also suggested a possible protective effect of mTORi in reducing the frequency of post transplant cancers.

[A case of intrarenal hematoma: role of ultrasonography in the early diagnosis of a possible complication of anticoagulant therapy]. / Un caso di ematoma intrarenale: ruolo degli ultrasuoni nella diagnosi in urgenza di una possibile complicanza del trattamento anticoagulante.

Uremia associated with anticoagulant therapy is a high risk factor for bleeding complications in patients undergoing hemodialysis. We report a case of intrarenal hematoma arising in a uremic patient treated with warfarin. The hematoma was rapidly diagnosed by ultrasonography of the abdomen and treated with embolization. Our experience confirms that the availability of an ultrasound facility within the renal unit allows better assessment of our patients, also in the management of the most fearsome and rare complications. Moreover, it strengthens the evidence that uremic patients are at high risk of bleeding complications when treated with oral anticoagulants.

Incidence of second primary cancer in transplanted patients.

BACKGROUND: Solid organ transplanted patients have a three- to fourfold higher lifetime risk of developing a cancer than the general population. However, the incidence of a second primary cancer in transplanted patients has never been studied, despite the fact that the presence of regular follow-ups and the increased survival of these patients make them a very attractive model. METHODS: We investigated the incidence of a second primary cancer (SPC) in 7,636 patients who underwent a kidney, liver, lung or heart transplant between 1970 and 2004, and were followed-up for 51,819 person-years. RESULTS: During the follow-up, 499 subjects developed a first cancer (annual incidence: 98.6 x 10,000 PY), and 22 of them developed a SPC (annual incidence: 3.9 x 10,000 PY). The annual incidence of a SPC in the transplanted patients who developed a first cancer was 107.8 x 10,000 PY, giving a standardized incidence ratio of 1.1 (95% CI: 0.83-1.41). CONCLUSIONS: This result shows that the incidence of the SPC was the same as the incidence of a first cancer. Our study does not indicate an increased risk of SPC in transplanted subjects who already suffered a first malignancy.

Relationship between plasma phospholipid polyunsaturated fatty acid composition and bone disease in renal transplantation.

To investigate the relationship between polyunsaturated fatty acid (PUFA) and bone metabolism in renal transplant patients, plasma phospholipid (PP) PUFA levels, biochemical markers of bone turnover and bone mineral density (BMD) were determined in 22 recipients of a first renal allograft at baseline and after a mean 24.4 month follow-up. A significant increase in PP n-3 PUFA content, in the [n-3 PUFA/ arachidonic acid] ratio and in BMD values was observed, as well as a close correlation between the increase in PP n-3 PUFA content and femoral neck BMD. Multivariate regression analysis showed that BMD improvement was positively related to PP n-3 PUFA variation and baseline PP eicosapentaenoic acid levels, and negatively to PP arachidonic acid modification. Tacrolimus- versus cyclosporine-treated patients demonstrated a significant increase in femoral neck BMD and PP n-3 PUFA content. This is the first longitudinal study showing a link between PP-PUFA composition and bone disease in renal transplantation.

Incidence of cancer after kidney transplant: results from the North Italy transplant program.

BACKGROUND: Patients undergoing kidney transplantation demonstrate a higher risk of developing cancer as the result of immunosuppressive treatment and concurrent infections. METHODS: The incidence of cancer in a cohort of patients who underwent kidney transplantation between 1990 and 2000, and who survived the acute phase (10 days), was analyzed as part of the North Italy Transplant program. RESULTS: A total of 3,521 patients underwent transplantation during a 10-year period in 10 of 13 participating centers; the length of follow-up after kidney transplant was 67.7+/-36.0 months. During the follow-up, 172 patients developed cancer (39 with Kaposi sarcoma, 38 with lymphoproliferative diseases, and 95 with carcinomas [17 kidney, 11 non-basal cell carcinoma of the skin, 10 colorectal, 8 breast, 7 gastric, 7 lung, 6 bladder, and 3 mesothelioma]). The average time to cancer development after transplant was 40.1+/-33.4 months (range 0-134 months). Twenty-four patients developed cancer within 6 months from the transplant (10 with carcinomas, 7 with Kaposi sarcoma, and 7 with lymphoproliferative diseases). Three patients demonstrated a second primary cancer. The average cancer incidence was 4.9%. The incidence of cancer was 0.01 per year. Independent determinants of cancer development were age, gender, and immunosuppressive protocol including induction. Ten-year mortality was significantly higher in patients with cancer (33.1%) than among patients without cancer (5.3%). The relative risk of death in subjects with cancer was 5.5 (confidence interval 4.1-7.4). CONCLUSIONS: These preliminary data underline the importance of long-term surveillance of transplant recipients, choice of immunosuppressive treatment, and careful donor selection.

Are the baseline chances of survival comparable between the candidates for kidney transplantation who actually receive a graft and those who never get one?

BACKGROUND: The superiority of kidney transplantation over dialysis for patient survival often is assessed by comparing the survival rate of candidates who get a graft to that of those on the waiting list who do not. This study tries to ascertain if the two groups are comparable in terms of their chances of surviving. METHODS: Of the 187 non-diabetic patients who entered our waiting list during 1998 and 1999 for first cadaveric kidney transplants, 81 received a graft and 106 did not. We compared the two groups for factors which could affect survival and that were present at the moment of acceptance on the list. As one of those factors was the clinical score quantifying health status, as given by the transplant team and rated from 1 (high risk) to 4 (very good), we assessed its reliability by evaluating the survival of the patients we transplanted between 1988 and 1996, grouped according to that score. RESULTS: Transplanted patients had been immunized less frequently (2 vs 13%; P=0.02), had a lower dialytic age (16.9+/-2.1 vs 22.9+/-2.1 months; P<0.05), and better clinical scores (2.9+/-0.1 vs 2.6+/-0.1; P<0.05). The two groups did not differ in age, gender, or the presence of single specific diseases. Logistic regression analysis confirmed the results of univariate analysis. The clinical score was a very strong predictor of patient survival, as the survival of patients transplanted from 1988 to 1996 progressively improved with better scores (P<0.0001). CONCLUSIONS: Transplanted patients actually differ from non-transplanted candidates with respect to various factors potentially affecting survival. The difference is highly relevant clinically, yet it is not easily detected when considering mainly the presence or absence of specific diseases. A global quantitative clinical parameter based on a thorough medical evaluation is required to identify differences.