Successful management of post-transplant focal segmental glomerulosclerosis with therapeutic plasma exchange and rituximab.

BACKGROUND: Post-transplant focal segmental glomerulosclerosis (FSGS) is associated with renal allograft loss. Currently, optimal treatment remains controversial. METHODS: The aim of our study was to examine the efficacy and safety of therapeutic plasma exchange (TPE), and rituximab (RTX), in the management of post-transplant FSGS. The treatment protocol consisted of RTX and monthly cycles of 5 plasma exchanges for 6 months. We treated 10 transplant recipients with biopsy-proven post-transplant FSGS. Lastly, we compared the studied group to a historic control group of nine patients with post-transplant FSGS. RESULTS: 9 out of 10 patients achieved remission after the conclusion of treatment (4 complete and 5 partial), while 1 patient did not respond to treatment. During the follow-up period, there was one graft loss and one patient died while in remission from unrelated complications. There was a significant reduction in mean uPCR between diagnosis (517.4 ± 524.2 mg/mmol) and last follow-up (87 ± 121.6 mg/mmol) in the patients with sustained remission (p = 0.026). There was no significant decline in eGFR in the eight relapse-free responders at the end of follow-up. (54.4 ± 16.7 from 49.8 ± 20.4 ml/min) (p = 0.6) An increased response rate to the combined TPE and RTX treatment was demonstrated, when compared to a historic control group of nine patients with post-transplant FSGS, as only five out of nine patients achieved remission (two complete and three partial) in that group. CONCLUSIONS: In this study, treatment with TPE and RTX appears to be safe, well tolerated and effective in the management of patients with post-transplant FSGS.

Effect of Smad pathway activation on podocyte cell cycle regulation: an immunohistochemical evaluation.

BACKGROUND: Mature podocytes are in cell cycle arrest and their inability to proliferate successfully is a consequence of negative cell-cycle regulators' expression, such as p57. Phosphorylated smad2/smad3 (pSmad2/3) is an intracellular heteromeric mediator of transforming growth factor beta (TGF-ß) signals and, together with co-activators such as P300, regulates gene transcription, including cell cycle regulator proteins. METHODS: In order to investigate Smad pathway activation and podocyte cell cycle regulation in glomerular injury, we studied the glomerular immunohistochemical expression of p57, pSmad2/3 and P300 in samples from 67 patients with various types of glomerulonephritis (GN) and 10 normal kidney tissue specimens. RESULTS: pSmad2/3 and p300 expression were found significantly increased in all glomerular cell types in both proliferative and nonproliferative GN, while a significant reduction in p57-positive podocytes was observed when compared to controls. Staining for p57 was found to inversely correlate to pSmad2/3 suggesting that glomerular Smad pathway activation is related to down-regulation of p57 expression in proliferative glomerulonephritis. To our knowledge, this is the first study that indicates a relation between the TGF-beta/Smad signalling pathway and the cell cycle regulatory protein p57 in human GN. CONCLUSION: The increased pSmad2/3 staining together with the reduced p57 expression found in biopsy specimens with intense interstitial inflammation, indicate a possible relation between interstitial inflammation, glomerular Smad pathway activation and podocyte cell-cycle deregulation.

A curious case of haemolysis, seizure and acute renal failure associated with pregnancy.

Differential diagnosis between thrombotic microangiopathies in pregnancy is challenging due to overlapping clinical and pathological findings and the rapid progression of disease. We present here an unusual case of Haemolysis, Elevated Liver enzymes and Low Platelets (HELLP) syndrome, which represents this diagnostic dilemma. The patient was treated with steroids and plasma exchange, leading to a favourable outcome. Subsequent genetic testing for complement dysregulation revealed a previously unknown variant in intron 3 of the gene coding for the alternative complement pathway factor H: (c.350+9T>C). We discuss here the diagnostic dilemma presented, the treatment pathway in the current literature, and the potential involvement of complement deregulation in severe HELLP. This case underlines the complexity in the diagnosis and management of pregnancy-related thrombotic microangiopathies.

The role of sympathetic nervous system in the progression of chronic kidney disease in the era of catheter based sympathetic renal denervation.

The kidney has been shown to be critically involved as both trigger and target of sympathetic nervous system overactivity in both experimental and clinical studies. Renal injury and ischemia, activation of renin angiotensin system and dysfunction of nitric oxide system have been implicated in adrenergic activation from kidney. Conversely, several lines of evidence suggest that sympathetic overactivity, through functional and morphological alterations in renal physiology and structure, may contribute to kidney injury and chronic kidney disease progression. Pharmacologic modulation of sympathetic nervous system activity has been found to have a blood pressure independent renoprotective effect. The inadequate normalization of sympathoexcitation by pharmacologic treatment asks for novel treatment options. Catheter based renal denervation targets selectively both efferent and afferent renal nerves and functionally denervates the kidney providing blood pressure reduction in clinical trials and renoprotection in experimental models by ameliorating the effects of excessive renal sympathetic drive. This review will focus on the role of sympathetic overactivity in the pathogenesis of kidney injury and CKD progression and will speculate on the effect of renal denervation to these conditions.

Neosartorya hiratsukae peritonitis through continuous ambulatory peritoneal dialysis.

Fungal peritonitis is a rare, potentially lethal, complication of continuous ambulatory peritoneal dialysis (CAPD). We report what we believe to be the first confirmed Neosartorya hiratsukae CAPD-related peritonitis case in Europe. The patient died, despite early removal of the peritoneal catheter and antifungal therapy. This report highlights the impact of emerging fungal pathogens and the importance of early diagnosis on the outcome in CAPD-related fungal peritonitis.

Simultaneous diagnosis of ulcerative jejunoileitis and coeliac disease in an elderly man.

Ulcerative jejunoileitis (UJI) is a rare condition which usually develops in patients with established or simultaneously diagnosed coeliac disease (CD) and has been suggested to represent cryptic low-grade enteropathy-associated T-cell lymphoma (EATL). We report a case of a 78-year-old male patient with UJI and CD diagnosed at the same time. He presented with abdominal pain, diarrhoea and weight loss and had serological, endoscopical, radiological and histological findings compatible with the diagnoses of both UJI and CD. The possibility of EATL was carefully excluded. The patient exhibited significant symptomatic improvement with a gluten-free diet, probably indicating an early stage of disease despite his old age. In conclusion, this rather unusual case of an elderly patient presenting with UJI and CD without evidence of EATL supports the great heterogeneity of these diseases not only in their clinical presentation but even in their course and complications.