For decades, ill-defined autosomal dominant renal diseases have been reported, which originate from tubular cells and lead to tubular atrophy and interstitial fibrosis. These diseases are clinically indistinguishable, but caused by mutations in at least four different genes: UMOD, HNF1B, REN, and, as recently described, MUC1. Affected family members show renal fibrosis in the biopsy and gradually declining renal function, with renal failure usually occurring between the third and sixth decade of life. Here we describe 10 families and define eligibility criteria to consider this type of inherited disease, as well as propose a practicable approach for diagnosis. In contrast to what the frequently used term 'Medullary Cystic Kidney Disease' implies, development of (medullary) cysts is neither an early nor a typical feature, as determined by MRI. In addition to Sanger and gene panel sequencing of the four genes, we established SNaPshot minisequencing for the predescribed cytosine duplication within a distinct repeat region of MUC1 causing a frameshift. A mutation was found in 7 of 9 families (3 in UMOD and 4 in MUC1), with one indeterminate (UMOD p.T62P). On the basis of clinical and pathological characteristics we propose the term 'Autosomal Dominant Tubulointerstitial Kidney Disease' as an improved terminology. This should enhance recognition and correct diagnosis of affected individuals, facilitate genetic counseling, and stimulate research into the underlying pathophysiology.

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age = 54 years, time immunosuppressed = 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio = 1.61, 95% confidence interval = [1.07, 2.43]), reported past skin cancer (prevalence ratio =3.39, 95% confidence interval = [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio = 1.76, 95% confidence interval = [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

This high-volume surgical outpatient transplant skin clinic enables efficient treatment of skin cancers in very-high-risk OTRs.

Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-␤, interleukin-10, and tumor necrosis factor ␣ (TNF-␣) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reactionbased methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P ‫؍‬ .001), immune-mediated liver disease (P ‫؍‬ .018), normal pre-OLT creatinine clearance (P ‫؍‬ .037), and fewer HLA class 1 mismatches (P ‫؍‬ .038) were independently associated with rejection. Renal impairment occurred in 80% of patients and was moderate or severe in 39%. Clinical variables independently associated with renal impairment were female sex (P ‫؍‬ .001), pre-OLT renal dysfunction (P ‫؍‬ .0001), and a diagnosis of viral hepatitis (P ‫؍‬ .0008). There was a significant difference in the frequency of TNF-␣-308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-␣-308 polymorphism and graft rejection approached significance (P ‫؍‬ .06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT. Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions. (Liver Transpl 2001;7:255-263.) S urvival after orthotopic liver transplantation (OLT) has steadily improved; overall 1-and 5-year patient survival rates for a primary graft are 88% and 74%, respectively. 1 Acute rejection occurs in up to 50% of patients but does not appear to adversely affect liver allograft survival. 2 Although current immunosuppressive regimens are very effective, concern is increasing about the side effects arising from long-term therapy. More than 50% of all deaths after OLT are caused by infection, 3 and approximately 4% of long-term survivors develop severe chronic renal failure. 4 These adverse consequences of immunosuppression may be reduced by modifying current drug regimens with lower doses of cyclosporine (CsA) and tacrolimus and earlier cessation of corticosteroid therapy. However, it remains difficult to predict the patients least likely to experience graft rejection who can be treated with minimal immunosuppression. In contrast to other solid organs, HLA matching for OLT has only a weak effect on rejection, and information...