Scoring system for renal pathology in Fabry disease: report of the International Study Group of Fabry Nephropathy (ISGFN).

BACKGROUND: In Fabry nephropathy, alpha-galactosidase deficiency leads to accumulation of glycosphingolipids in all kidney cell types, proteinuria and progressive loss of kidney function. METHODS: An international working group of nephrologists from 11 Fabry centres identified adult Fabry patients, and pathologists scored histologic changes on renal biopsies. A standardized scoring system was developed with a modified Delphi technique assessing 59 Fabry nephropathy cases. Each case was scored independently of clinical information by at least three pathologists with an average final score reported. RESULTS: We assessed 35 males (mean age 36.4 years) and 24 females (43.9 years) who mostly had clinically mild Fabry nephropathy. The average serum creatinine was 1.3 mg/dl (114.9 micromol/l); estimated glomerular filtration rate was 81.7 ml/min/1.73 m(2) and urine protein to creatinine ratio was 1.08 g/g (122.0 mg/mmol). Males had greater podocyte vacuolization on light microscopy (mean score) and glycosphingolipid inclusions on semi-thin sections than females. Males also had significantly more proximal tubule, peritubular capillary and vascular intimal inclusions. Arteriolar hyalinosis was similar, but females had significantly more arterial hyalinosis. Chronic kidney disease stage correlated with arterial and glomerular sclerosis scores. Significant changes, including segmental and global sclerosis, and interstitial fibrosis were seen even in patients with stage 1-2 chronic kidney disease with minimal proteinuria. CONCLUSIONS: The development of a standardized scoring system of both disease-specific lesions, i.e. lipid deposition related, and general lesions of progression, i.e. fibrosis and sclerosis, showed a spectrum of histologic appearances even in early clinical stage of Fabry nephropathy. These findings support the role of kidney biopsy in the baseline evaluation of Fabry nephropathy, even with mild clinical disease. The scoring system will be useful for longitudinal assessment of prognosis and responses to therapy for Fabry nephropathy.

Challenges in diagnosing acute pancreatitis in renal transplant patients.

Acute pancreatitis is a recognized occurrence in patients with end-stage renal disease, those on dialysis and those who have undergone renal transplantation. The incidence is significantly increased in comparison to the general population and carries significant mortality. We report two cases of acute pancreatitis that occurred in stable renal transplant recipients, and in which there was diagnostic difficulty. The etiology of the acute pancreatitis is not always identifiable in these patients. Classical symptoms and laboratory findings are often absent, which may cause diagnostic difficulty. Our experience suggests that in immunosuppressed patients with unexplained abdominal pain or abnormal liver function tests, acute pancreatitis should be considered at an early stage in order to initiate appropriate treatment and therefore minimize mortality and morbidity.

Occult splenic rupture with cardiovascular collapse: a report of three cases in critically ill patients.

Three cases of splenic rupture causing cardiovascular collapse in critically ill patients are discussed. The first patient had received cardiopulmonary resuscitation (CPR) in the days before the collapse, the second patient was recovering from severe sepsis and the third patient was recovering from severe sepsis, had received CPR and had undergone percutaneous endoscopic gastrostomy (PEG). The diagnosis was made at post mortem in two of the patients, the third patient, who bled following PEG, survived after prompt surgical intervention. Splenic rupture should be considered as part of the differential diagnosis of unexpected cardiovascular collapse in patients who have received CPR or who are recovering from sepsis.

Carcinoid tumor originating in a horseshoe kidney.

An atypical carcinoid tumor originating in the horseshoe kidney of a 39-year-old man is reported. The tumor showed cytological atypia, increased mitotic rate and histological signs of mucinous differentiation and osseous metaplasia. Even though there were distant metastases, the patient survived partial nephrectomy including resection of the primary tumor for four years. The review of literature shows that carcinoid tumors originate some 60 to 85 times more often in horseshoe kidneys than in normal kidneys. The clinical course of renal carcinoid tumors is highly variable.

Kikuchi disease preceding systemic lupus erythematosus with membranous lupus nephritis.

Kikuchi disease (KD) is a rare form of necrotizing lymphadenitis. KD usually presents with cervical lymphadenopathy and fever in young women. It tends to run a benign course and resolve spontaneously within months. The aetiology of the disease is still unclear although a variety of infectious agents have been postulated. There is also a documented but rare association with systemic lupus erythematosus (SLE). We present the case of a young woman with biopsy-proven KD who subsequently developed SLE with biopsy-proven lupus nephritis. Nephrologists should be aware of KD as it may precede the development of SLE and lupus nephritis.

Acute renal failure, systemic lupus erythematosus and thrombotic microangiopathy following treatment with beta-interferon for multiple sclerosis: case report and review of the literature.

We report a man with type 1 diabetes mellitus, autoimmune hypothyroidism and a tentative diagnosis of multiple sclerosis. Following treatment with beta interferon, he developed systemic lupus erythematosus with pericarditis, pleural effusions, cerebral infarction associated with anti-phospholipid antibody and acute renal failure due to thrombotic microangiopathy. He responded well to immunosuppression and anticoagulation. These complications may represent the most severe autoimmune reaction to beta interferon reported to date.

Determinants of renal functional outcome in lupus nephritis: a single centre retrospective study.

BACKGROUND: Lupus nephritis (LN) is a rare disease but is the strongest predictor of poor outcome in patients with Systemic Lupus Erythematosis (SLE). It is associated with significant morbidity, with 10-20% of patients developing end stage renal failure. As there is a paucity of randomized clinical trial data in LN, and no consistent literature regarding baseline factors that predict renal outcome, we were prompted to analyse our centre's complete experience of managing LN. METHODS: A retrospective analysis was undertaken of all patients presenting to our renal centre with biopsy proven LN from 1979-2003. Patients were divided into two categories, those with stable or deteriorating renal function over time. Baseline parameters were correlated with renal outcome. RESULTS: Complete clinical records were available for 45 (40 female) patients. Mean (SD) age of onset of SLE was 32 +/- 14 years, and mean age onset of LN was 36 +/- 13 years. Patients were followed up for an average of 74 +/- 56 months. Four patients (9%) had WHO Class II LN, 11 (24%) WHO Class III and there were 15 (33%) each in Class IV and V, respectively on renal biopsy. Five (11%) patients presented with acute renal failure and all had proliferative changes on biopsy. The chief arbiters of renal functional deterioration over follow up were longer time to development of LN (P = 0.04), a high platelet count and worse baseline renal function (both P = 0.05). There was a trend relating low haemoglobin or membranous histology to poor renal outcome, and Class IV histology to better outcome. CONCLUSION: The study has identified that longer time to development of LN, high platelet count and poorer renal function at baseline suggest a worse renal outcome in LN. The study was small but LN is a rare condition. A combination of factors is likely to influence renal outcome in LN and larger prospective trials are required to ascertain consistent baseline prognostic markers.

A correlation of FTIR spectra derived from prostate cancer biopsies with gleason grade and tumour stage.

OBJECTIVES: We introduce biochemistry as a second dimension to Gleason grading, using Fourier transform infrared (FTIR) microspectroscopy. For the first time, we correlate FTIR spectra derived from prostate cancer (pCA) tissue with Gleason score and the clinical stage of the tumour at time of biopsy. METHODS: Serial sections from paraffin-embedded pCA tissue were collected. One was stained with hematoxylin and eosin and Gleason scored; FTIR spectra were collected from malignant locations using a second unstained section. FTIR spectra, representing different Gleason grades, were used to construct a diagnostic classifier for pCA using linear discriminant analysis (LDA). This model was blind tested using 383 IR spectra from 36 biopsies. RESULTS: Using a three-band Gleason criteria, we obtained sensitivity of > or =70% for the FTIR-LDA model to predict Gleason <7,=7, and >7, with specificities of > or =81%. Using a threshold of Gleason/FTIR-LDA score of > or =8, we obtained a sensitivity and specificity of 71% and 67%, respectively, for the correlation with metastatic tumours using the FTIR-LDA system and 85% and 63%, respectively, for the correlation of metastatic tumours using the Gleason system. CONCLUSIONS: There is a correlation between tissue architecture using Gleason score with tissue biochemistry using FTIR-LDA. Both systems are similar in their performance in predicting metastatic behaviour in tumours from individual patients.

Male adnexal tumour of probable Wolffian duct origin.

Male adnexal tumours of Wolffian duct origin are very rare. They have variable malignant potential and surgical excision is recommended. We report the case of a 56-year-old male who presented with a swelling in the perineum thought to be a haematoma as the result of a complication of a laparoscopic inguinal hernia repair. It recurred after incision and two attempts at drainage and was then completely excised. Histology revealed the lesion to be an adnexal tumour of probable Wolffian duct origin. To our knowledge there have only been two previous cases of male adnexal tumour of Wolffian duct origin reported in the literature.