Cancer mortality after kidney transplantation: A multicenter cohort study in Italy.

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients.

The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients.

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.

Variation in Post-Transplant Cancer Incidence among Italian Kidney Transplant Recipients over a 25-Year Period.

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997-2004 to 21.0 in 2013-2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76-1.07 in 2005-2012; IRR = 0.72, 95% CI: 0.60-0.87 in 2013-2021 vs. 1997-2004; Ptrend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24-0.57 in 2005-2012; IRR = 0.09, 95% CI: 0.04-0.18 in 2013-2021; Ptrend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26-2.85 in 1997-2004; SIR = 1.99, 95% CI: 1.83-2.16 in 2013-2021; Ptrend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

[Skin cancer in renal transplant recipients]. / Le neoplasie della cute nel paziente trapiantato.

Kidney transplant is the best treatment option for renal failure. Over the years the 1-year patient survival has gradually increased, along with a reduction in acute rejection. The main causes of death in the late post-transplant period are cardiovascular disease, infections and malignancies. It is known that the incidence of cancer increases with the duration of post-transplant follow-up. Twenty years after transplantation, approximately 70% of patients on continuous immunosuppressive therapy present one or more tumor types. Some of the tumors that occur with a significantly higher frequency in transplant recipients compared with the general population are often associated with the reactivation of oncogenic viruses. Examples are herpes virus 8 (HHV8), implicated in Kaposi's sarcoma (KS), human papillomavirus (HPV), involved in squamous cell cancer of the skin, vulva, vagina and cervix, and Epstein-Barr virus (EBV), responsible for post-transplant lymphoproliferative disorder (PTLD). The type of drug used for the induction and maintenance of immunosuppression and the duration of treatment influence both the incidence and the type of cancer. For this reason, post-transplant malignancies often show a more aggressive behavior than tumors in the normal population. It is estimated that sarcomas occur 40 to 250 times more frequently in transplant recipients and are the leading cause of death from skin cancer after transplantation. The classic form of KS occurs in males and homosexuals. In the population of the Mediterranean area, KS is often associated with HHV8 infection that is reactivated by immunosuppression. The reduction or suspension of immunosuppressive therapy is the first step in the treatment of post-transplant KS. The second approach is chemotherapy. Since m-TOR, the target of sirolimus, is altered in many tumors, sirolimus may be an effective tool. Sirolimus inhibits not only cell proliferation but also tumor neovascularization by reducing VEGF production and inhibiting VEGF receptor signaling in endothelial cells. In conclusion, new strategies must be developed to reduce cancer mortality in transplant recipients while ensuring adequate immunosuppression to preserve the transplanted organ. One such strategy is the adoption of immunosuppressive regimens tailored to individual patients' medical history.

[From pharmacogenetics to pharmacogenomics: the start of a new era of personalized medicine in nephrology]. / Dalla farmacogenetica alla farmacogenomica: la nuova era della terapia personalizzata in nefrologia.

Recent evidence suggests that adverse drug reactions are a major cause of death and hospital admissions in Europe and the United States. Environmental/ non-genetic as well as genetic factors are responsible for the great interpatient variability in drug metabolism and in the molecular interactions between drugs and therapeutic targets. By means of pharmacogenetic approaches, several genetic settings have been linked to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, which analyze single genes or candidate pathways, cannot be considered ideal because the overall pharmacological effects of drugs typically are not dependent on monogenic traits. Therefore, to identify the multigenetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole-genome, high-throughput technologies. In nephrology, only few pharmacogenomics reports have been published to date, suggesting the need to enlarge the number of projects and increase the research budget for this important research field. In the future, we would expect that by applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic makeup, to carefully monitor the efficacy and toxicity of a given drug, and to modify the dose and number of medications to obtain predefined clinical outcomes.

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.