Cancer Incidence and Survival in Kidney Transplant Patients

Immunosuppression after organ transplantation is associated with a markedly increased risk of nonmelanoma skin cancer (NMSC) and malignancies, including posttransplant lymphoproliferative disorder (PTLD) and solid organ cancer. This study sought to investigate the incidence of malignancies and the clinical characteristics and risk factors of the renal transplant patients with solid organ tumors and NMSC. We included 1017 patients who received a kidney transplant in our hospital from 1979 to 2007. Results were contrasted with a cohort of patients from the same center without malignancies. The mean follow-up of patients in our series was 10 years. The mean age at presentation of the malignancy was 61 ± 5 years. The malignancy and NMSC incidences were 6% and 5%, respectively. Patients with malignancy had a longer posttransplant time and greater recipient and donor age. In the multivariate analysis, independent risk factors for developing NMSC were: male sex (hazard ratio [HR] 3.1, P = .004); greater patient age (HR 1.09, P < .001), longer posttransplant time (HR 1.2, P = .004) and tacrolimus treatment (HR 4.4, P = .001). Risk factors associated with developing any malignancy were: patient age (HR 1.06, P < .001), number of grafts (HR 3.2, P = .019), tacrolimus treatment (HR 2.5, P = .035), and time posttransplantation (HR 1.2, P = .011). The mean times to development of an NMSC, solid organ malignancy, on PTLD were 7.5, 6.1, or 3.9 years, respectively. The mean survival time from the diagnosis of any malignancy was 9.6 months (95% confidence interval, 0.12-30) for solid organ malignancies and 1 month (95% confidence interval, 0.24-1.87) for PTLD.     

Therapeutic interventions for autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening hereditary disease in the United States and causes end-stage renal failure requiring dialysis and renal transplantation. There is no effective treatment for ADPKD in humans. However, there are now multiple clinical trials testing a host of therapeutic interventions in children and adults with ADPKD. The major therapeutic interventions being tested in patients with ADPKD include Tolvaptan, Octreotide, Sirolimus, Everolimus, and statins, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).     

Autosomal dominant polycystic kidney disease in a kidney transplant population

AIM: To define specific manifestations of autosomal dominant polycystic kidney disease in kidney transplant patients. METHODS: Of 874 consecutive first renal transplant patients 1985-1993, 114 (13%) had autosomal dominant polycystic kidney disease (ADPKD). Mean age was 53 +/- 8 years, 62% were men, and 83% received cadaveric kidneys. Control patients were matched for sex, age and donor type. Median follow-up time was 63 months. One patient was lost to follow-up. Medical records before and after transplantation were reviewed. RESULTS: Survival of patients and grafts was similar in ADPKD patients and controls. Twenty- five ADPKD patients died, four of causes not seen in the controls; two aortic aneurysms, one urothelial cancer, one colon perforation. Four more ADPKD patients but no control had diverticulitis (P = 0.03), two with perforation. Cardiovascular morbidity was not increased. Eight patients had subarachnoidal haemorrhage before transplantation and two during follow-up. Nineteen patients had undergone nephrectomy before transplantation, 11 because of voluminous kidneys, five for infection, pain or bleeding, two for suspected malignancy, one for hypertension. After transplantation, seven patients underwent nephrectomy, only one related to kidney size. During the first year, need of phlebotomy occurred in 14% of patients versus 4% of controls, P = 0.02. Urinary tract infection rates were not increased. No morbidity was related to liver cysts. CONCLUSION: The specific features of kidney transplantation to patients with ADPKD were few: enlarged kidneys, relevant only before transplantation, erythrocytosis, and as rare but serious events, diverticulitis with perforation.      

The association between autosomal dominant polycystic kidney disease and cancer

International Urology and Nephrology - Autosomal dominant polycystic kidney disease (ADPKD) is considered as a tumor-like disease because there are many biological similarities between ADPKD and...     

Renal transplantation in patients with autosomal dominant polycystic kidney disease: pre-transplantation evaluation and follow-up

Autosomal dominant polycystic kidney disease (ADPKD) which accounts for 15% of all renal transplantations emerges as the third cause of kidney transplantation in France. In addition to routine evaluation before transplantation, the ADPKD patient requires special assessment of three aspects: should potential kidney complications (recurrent upper tract infection or haemorrhage) or kidney size assessed by computed tomography require nephrectomy prior to transplantation? Is it advisable to detect intracranial aneurysm (ICA) in patients with a relative having experienced ruptured ICA? When transplantation from a living relative is considered, the existence of ADPKD in the donor should be formally ruled out by imaging or genetic studies. The risk of recurrence of ADPKD post-transplantation does not exist. Nevertheless other complications may occur. Thus, an increased incidence of colonic perforation has been reported. In addition, as compared to non-ADPKD patients, an increased risk for both skin cancer and new-onset post-transplant diabetes mellitus has been reported recently after kidney transplantation. Finally, because these patients suffer from an inherited syndrome, physicians should carefully consider the personal and familial history before and after transplantation in order to respond to fatalism in some cases, or to attenuate excessive enthusiasm in the others. Altogether, it apears that a specific approach is needed for ADPKD patients when considering renal transplantation.     

Natural-derived compounds and their mechanisms in potential autosomal dominant polycystic kidney disease (ADPKD) treatment

Clinical and Experimental Nephrology - Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic kidney disorder that impairs renal functions progressively leading to kidney failure. The...     

Putative mutation of PKD1 gene responsible for autosomal dominant polycystic kidney disease in a Chinese family

Autosomal dominant polycystic kidney disease (ADPKD) is a common and severe renal disease. Mutations of PKD1 and PKD2 genes are responsible for approximately 85% and 15% of ADPKD cases, respectively. In the present study, PKD1 and PKD2 genes were analyzed in a large Chinese family with ADPKD using denaturing high‐performance liquid chromatography and DNA sequencing. A novel mutation, c.3623‐3624insGTGT in exon 15 of the PKD1 gene, was identified in all nine affected family members, but not in any unaffected consanguineous relatives or 100 unrelated controls. These findings suggest that the unique 4 bp insertion, c.3623‐3624insGTGT, in the PKD1 gene might be the pathogenic mutation responsible for the disease in this family.     

Multiple intracranial aneurysms in a patient with autosomal recessive polycystic kidney disease.

Autosomal recessive polycystic kidney disease (ARPKD) is usually characterized by early onset chronic renal failure due to innumerable dilated collecting ducts. Hepatic fibrosis is an obligate sign. Here, for the first time, we report a 31-year-old female with ARPKD who was diagnosed with symptomatic multiple intracranial aneurysms, a manifestation previously only known to be associated with autosomal dominant polycystic kidney disease (ADPKD).     

Clinical problems in hemodialysis patients with autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD ) is a common monogenic disease characterized by massive enlargement of fluid‐filled cysts in the kidney. Due to its genetic pattern, the disease differs from other CKD. ADPKD is a multi‐system, progressive disorder which is frequently complicated with hypertension, cardiovascular events and cerebrovascular disease. Thus, there are many clinical problems specific to ADPKD . In this article, we reviewed these clinical problems and their management in ADPKD with hemodialysis patients.     

Lymphoma after living donor kidney transplantation: an Iranian multicenter experience

Introduction  Post-transplant lymphoproliferative disorders (PTLD) are well-recognized complications in solid organ recipients. Limited data exist about the development of PTLDs in living kidney recipients. This study deals with a multicenter nationwide experience with kidney recipients from living donors. Methods  We reviewed data of PTLD patients from a total population of 6,500 patients transplanted at three different transplant centers in Iran from 1984 to 2006. We also compared their data with 2,250 normal kidney recipients of Baqiyatallah Transplant Center. Data were analyzed to determine potential correlates with the occurrence of PTLD and patient outcome. Results  Overall, 31 patients were diagnosed as having post-transplant lymphomas. The incidence of PTLD in our kidney transplant population comprised 0.47%. Sixteen (53%) PTLD patients were females, whereas 15 (47%) were males. The mean ages at transplantation and diagnosis were 37.1 and 41.9, respectively. Twelve (63%) patients died, and seven are alive. All deaths occurred within the 1st year after PTLD diagnosis. The mean time period from transplantation to diagnosis of PTLD was 64 (0.7–173) months. Localization of PTLD in the brain associated the worst outcome. Compared to non-PTLD patients, PTLD patients were significantly female predominated (51.6% vs. 32.2%; P = 0.03) and had lower age at transplantation (36.9 years vs. 42.9 years, respectively; P = 0.01). Patients under immunosuppressive regimens containing azathioprine were at higher risk for acquiring PTLDs compared to those with a MMF-containing regimen. Conclusion  PTLD is a major threat to kidney transplant recipients. Immunosuppressive agents have a significant role in developing the disease. Early detection of the disease and using more safe immunosuppresants may have beneficial effects on patient outcomes and incidence of the disease.     

The prevalence of seminal vesicle cysts in autosomal dominant polycystic kidney disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a systemic hereditary disorder characterized by bilateral diffuse renal cysts. Extrarenal involvement is a well known manifestation of ADPKD. Data relating to the association between seminal vesicle cysts and ADPKD are limited. The aims of this study are to evaluate the frequency of seminal vesicle cysts in ADPKD and to assess the relationship between seminal vesicle cysts, with cysts in the liver and prostate, and creatininaemia. Methods: Forty five male patients (mean age 40 years, range 13-67) were included in the study. Each subject underwent a formal interview, physical examination; and abdominal and transrectal ultrasonography. Three patients were infertile, but one of the patients also had varicocele. Results: Seminal vesicle cysts were present in 27 (60%) patients. Liver and prostate cysts were present in 19 (42%) and five (11%) patients, respectively. There was a positive correlation between seminal vesicle cysts, cysts in the liver, and serum creatinine concentrations. Conclusion: Our conclusions are: (i) seminal vesicle cysts are not uncommon in ADPKD; (II) ADPKD should be looked for in patients with seminal vesicle cysts, and (iii) the clinical significance of seminal vesicle cysts in ADPKD remains to be defined.     

Mutations in multiple PKD genes may explain early and severe polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is typically a late-onset disease caused by mutations in PKD1 or PKD2, but about 2% of patients with ADPKD show an early and severe phenotype that can be clinically indistinguishable from autosomal recessive polycystic kidney disease (ARPKD). The high recurrence risk in pedigrees with early and severe PKD strongly suggests a common familial modifying background, but the mechanisms underlying the extensive phenotypic variability observed among affected family members remain unknown. Here, we describe severely affected patients with PKD who carry, in addition to their expected familial germ-line defect, additional mutations in PKD genes, including HNF-1β, which likely aggravate the phenotype. Our findings are consistent with a common pathogenesis and dosage theory for PKD and may propose a general concept for the modification of disease expression in other so-called monogenic disorders.     

Polycystic kidney diseases: molecular genetics and counselling

Autosomal dominant polycystic kidney disease (ADPKD) affects 1 newborn in 400 to 1000 making it the most common inherited form of genetic kidney disease and an important cause of medical morbidity and account for about 10% of end-stage renal disease. Autosomal recessive polycystic kidney disease (ARPKD) is a rare (1/20,000 to 1/40,000) inherited disease in children characterized by the association of dilation of collecting ducts and biliary dysgenesis. The clinical spectrum is variable but it represents an important cause of renal and liver-related morbidity and mortality in neonates and infancy. Symptoms of autosomal recessive PKD can begin before birth. ARPKD is genetically different from ADPKD. Parents who do not have the disease can have a child with the disease if both parents carry the abnormal gene and both pass the gene to their baby. Recently important advances in understanding the molecular basis of ADPKD (i.e. ADPKD1 and ADPKD2) and autosomal recessive PKD (i.e. PKHD1) have been done and are reported here. Genetic counselling is particularly advised in early onset disease families. It permits to determine the type of transmission, to describe the course and the major complications of the disease and to explain currents therapeutics possibilities.     

Autosomal Dominant Polycystic Kidney Disease Transplant Recipients After Kidney Transplantation: A Single-center Experience

Kidney transplantation is indicated for end-stage renal disease. Autosomal dominant polycystic kidney disease (ADPKD) causes structural degeneration of the kidney and eventually becomes end-stage renal disease. ADPKD patients usually have several renal and nonrenal complications. We analyzed our kidney transplantation activities between 1991 and 2010 regarding ADPKD. We followed up with patients to December 31, 2016. Data were collected as patient and graft survival rates, the prevalence of polycystic manifestation of the gastrointestinal tract and other organs, and the attendance of urinary tract infection. Among the 734 kidney transplantations, 10.9% (n = 80) had an ADPKD. Four patients (5%) had diverticulum perforation. The prevalence of post-transplantation urinary tract infection was higher in ADPKD patients (55.9%) compared to non-ADPKD patients (44.1%). The 1-, 3-, and 5-year overall survival rates in ADPKD recipients versus non-ADPKD patients are 77.5%, 70.0%, and 67.5% versus 86.4%, 83.0%, and 80.1%, respectively. Patients with ADPKD were transplanted at an elder age compared to others (median: 47.5 years vs. 39.9 years). Female patients had longer graft survival times than males. ADPKD implies multiple cystic degeneration of the kidneys; however, it can cause structural degeneration in other organs. It is typical for ADPKD patients to have an acute abdominal-like syndrome. Immunosuppressive drugs can hide the clinical picture, which makes early diagnosis difficult.     

Ambulatory blood pressure in hypertensive patients with autosomal dominant polycystic kidney disease

Background: Ambulatory blood pressure is more closely correlated with various indices of hypertensive target-organ damage, and is a better prognostic predictor of cardiovascular morbidity and mortality than conventional methods of blood pressure measurement. Autosomal dominant polycystic kidney disease (ADPKD) is complicated by hypertension, progressive renal failure, and an increased risk of cardiovascular mortality. This study investigated the 24-h ambulatory blood pressure profile in patients with ADPKD in view of the sparsity of such data in these patients and the possibility that abnormal diurnal blood pressure variations may have prognostic consequences. Methods: Ambulatory blood pressure was measured over a 24-h period by the oscillometric method with an automatic non-invasive recorder (SpaceLabs 90207 system) in matched groups of 25 hypertensive patients with ADPKD and 25 patients with essential hypertension. Results: Both groups showed a nocturnal decrease in blood pressure, but this was significantly smaller in patients with ADPKD. There was no evidence of enhanced lability of blood pressure in ADPKD. Conclusion: The nocturnal fall in blood pressure was attenuated in patients with ADPKD. Further studies are required to assess the importance of this finding and its possible contribution to the progression of renal failure or increased cardiovascular mortality in these patients.     

Urinary tract infections,VUR, and autosomal dominant polycystic kidney disease

This case series of 16 patients with autosomal dominant polycystic kidney disease (ADPKD) describes 4 girls who presented with a urinary tract infection (UTI). Radiological evaluation revealed that each of these patients had vesicoureteral reflux (VUR). The frequency of VUR was significantly higher in the patients with ADPKD compared with otherwise healthy age-matched children who underwent testing after a UTI (100% versus 15%, P<0.002). These findings suggest VUR is an associated somatic anomaly in children with ADPKD that may contribute to the occurrence of UTI in this patient population.     

Neonatal presentation of autosomal dominant polycystic kidney disease with a maternal history of tuberous sclerosis

Background: Childhood presentation of polycystic kidney disease has been reported with tuberous sclerosis complex (TSC). Recently some such cases have been shown to be due to combined deletion of the PKD1 and TSC2 genes, which lie close together on chromosome 16. The phenomenon of anticipation, whereby disease presentation occurs at a progressively earlier age in each generation, has been suggested to occur in autosomal dominant polycystic kidney disease (ADPKD). We have carried out a genetic study of a family in which these issues became clinically relevant. Neonatal presentation of polycystic kidneys occurred in an individual with a maternal family history of epilepsy and features of TSC without renal cystic disease. Method: Detailed historical and clinical profiles were gathered for three generations of the maternal and paternal families. Both parents underwent renal ultrasound scanning. Genomic DNA was obtained from affected and unaffected individuals from the maternal family and used for linkage analysis to gene loci for TSC. Results: Renal cysts were not present in the mother by ultrasound. Linkage to TSC2 was found for members of the maternal family with clinical features of TSC. While a diagnosis of TSC was confirmed in her mother the child was found not to have inherited the disease-related allele. The father was found to have asymptomatic bilateral polycystic kidneys consistent with ADPKD. The presence of ADPKD in other paternal relatives could not be confirmed. Conclusions: The index case was found to have paternally inherited ADPKD with unusually early presentation. While at risk for concomitant maternal inheritance of TSC this diagnosis was ruled out by linkage analysis studies. The ability to clarify the true nature of a complex inherited condition greatly facilitates future management and counselling. The mechanisms underlying phenotypic heterogeneity in ADPKD remain to be clearly defined and are the subject of ongoing investigation.     

Center is an important indicator for choice of invasive therapy in polycystic liver disease

Polycystic liver disease (PLD) is a rare genetic disorder with progressive cyst growth as the primary phenotype. Therapy consists of volume reduction through invasive surgical or radiological procedures. To understand the process of treatment decision, our aim was to identify factors that increased the likelihood of treatment. We performed a cross‐sectional study using an international population of patients with PLD. We collected data on the following therapies: liver transplantation, resection, fenestration, and aspiration sclerotherapy. Data on the potential determinants, sex, center, autosomal dominant polycystic kidney disease (ADPKD), autosomal dominant polycystic liver disease (ADPLD), age at diagnosis, symptoms, and phenotype, were included. We corrected for follow‐up time. We included 578 patients in our study, and 35% underwent invasive therapy. Multivariate regression analysis showed that number of symptoms and age at diagnosis of PLD increased the likelihood of treatment (respectively, RR: 1.4, P < 0.001 and RR = 1.4, P = 0.03). The choice for liver transplantation or aspiration sclerotherapy was center dependent (RR: 0.7, P < 0.001 and RR: 1.1, P = 0.03, respectively). The results of our international cross‐sectional study suggest that a higher number of symptoms and every 10 years of PLD diagnosis increase the risk to undergo treatment by 40%. The choice to elect a particular modality is center dependent.     

Urinary citrate as a marker of renal function in patients with autosomal dominant polycystic kidney disease

International Urology and Nephrology - Autosomal dominant polycystic kidney disease (ADPKD) is frequent to find low urinary citrate levels. Recently, it has been suggested that urinary citrate...     

Effect of tolvaptan in Japanese patients with autosomal dominant polycystic kidney disease: a post hoc analysis of TEMPO 3:4 and TEMPO Extension Japan

Clinical and Experimental Nephrology - Autosomal dominant polycystic kidney disease (ADPKD) is a progressive condition that eventually leads to end-stage renal disease. A phase 3 trial of tolvaptan...