We report a case of a 67-year-old man who experienced allograft dysfunction following a renal transplantation from a donation after cardiac death. The postoperative course was initially complicated by episodes of E. coli urinary sepsis causing pyrexia and a raised creatinine level. Ultrasound scanning 5 weeks posttransplant revealed mild hydronephrosis with several parenchymal cystic areas measuring up to 2 cm with appearances suggestive of fungal balls. Aspirated fluid again grew Escherichia coli, and this was treated with the appropriate antimicrobial therapy. The patient continued to have episodes of culture-negative sepsis; therefore, a computed tomography scan was performed 6 months posttransplant, which revealed multiple lesions in the renal cortex as well as liver and spleen. Subsequent biopsy revealed an Epstein-Barr virus-driven lymphoproliferation consistent with a polymorphic posttransplantation lymphoproliferative disorder (PTLD). This rare case of PTLD presenting as multiple renal, hepatic and splenic lesions emphasizes the need for a high index of clinical suspicion for this condition. Abnormal para-renal allograft masses should be biopsied to allow swift and effective management of a disease that can disseminate and become significantly more challenging to manage.

Background Understanding the pathogenesis of the autosomal recessive cystic kidney disease, nephronophthisis (NPHP) remains a challenge. NPHP is associated with extra-renal disease in 10-15%, including abnormal eye and cerebellar development, this combination of problems is called Joubert Syndrome, JS. NPHP and JS are ciliopathies because the encoded proteins of all mutated genes are found in primary cilia/associated architecture. NPHP and JS are genetically heterogenous, with mutations in a single gene such as NPHP6, AHI1 or CC2D2A being sufficient to cause disease. Although homozygous mutations are identified in most cases, some patients have an additional heterozygous mutation in another gene, leading to hypotheses of epistasis modifying the clinical phenotype.

Joubert syndrome (JBTS) is an inherited ciliopathy leading to a cerebellum-retinal-renal syndrome.Recent genetic advances have allowed positional cloning and identification of numerous JBTS genes.CEP290, one of the JBTS genes identified, (alias NPHP6) encodes a centrosomal protein and accounts for 7% of patients with Joubert syndrome.We have identified a murine Embryonic Stem (ES) cell line containing a Cep290 "gene trap" using data base searches.ES cells were cultured before injecting into murine blastocysts to create chimaeric mice.Chimeras were bred to produce viable, healthy heterozygous mutant mice.Heterozygous mutant mice have been intercrossed to produce mice homozygous for the Cep290 truncating mutation.Cep290-/animals (homozygous for the gene trap Cep290) exhibit a cortico-medullary cystic kidney disease commencing from birth.Histological examination reveals that these cysts are collecting duct in origin, staining positively for aquaporin-2 and -3.In this study the cilia were investigated in cystic Cep290-/animals using Electron Microscopy (EM) analysis.Scanning electron microscopy (SEM) identified that cilia were evident within renal tubules in Cep290-/animals.Once cilia were identified in Cep290-/animals Transmission Electron Microscopy (TEM) was carried out to investigate cross sections of the collecting duct cilium in cystic and non-cystic kidneys.TEM analysis identified tubular basement membrane disruptions in Cep290-/animals.The Cep290-/mouse described provides an excellent model to investigate the mechanisms involved in cyst formation and to test novel therapeutic agents.

A 38-year-old lady (III.1 in Figure 1) was referred to the nephrology services with an increase in her plasma creatinine from 108 μmol/l [normal range (NR) 49–90 μmol/l] to 147 μmol/l over a 5-year period. She had previously been seen by a nephrologist at the age of 19 years when an abdominal ultrasound scan (USS) had shown a dysplastic left kidney as an incidental finding. At that time, an isotope renogram showed preserved function of the right kidney, while the left kidney contributed only 24% of total renal function. There was no history of urinary infection, she was normotensive and 24-h protein excretion was 11.1 mmol/l) at 2 h. She was also affected by congenital combined growth hormone (GH) and gonadotrophin hormone deficiencies, with a small pituitary on MR imaging. Abdominal USS at the age of 19 demonstrated an infantile uterus, and unidentifiable ovaries, consistent with her prepubertal status at the time. Figure 1. Pedigree, clinical characteristics and genotype of family. Age in years of diagnosis of diabetes, where known. Asterisk indicates HNF1A mutation P291fsinsC identified. Key: shading top left (diabetes), top right (renal dysplasia), bottom right (growth hormone deficiency), bottom left (hypothyroid). On clinical review, there was no evidence of diabetic retinopathy or neuropathy. Medications included …