Hepatitis B vaccination in haemodialysis patients: an underestimated problem. Factors influencing immune responses in ten years of observation in an Italian haemodialysis centre and literature review.

OBJECTIVES: Despite universal infection control precautions, the risk of hepatitis B virus (HBV) infection in patients on chronic haemodialysis (HD) remains high. For this reason anti-HBV vaccination is recommended in these subjects. In hemodialyzed patients vaccinal response is often suboptimal and it's not clear what factors may influence it. STUDY DESIGN: The aim of our study is to assess the influence of some clinical and laboratory factors on seroconversion rate after anti HBV vaccination in a cohort of patients on maintenance HD. METHODS: We analysed 60 patients on regular HD, 40 men and 20 women (age 64±12 years, range 40-88 years), immunized with Engerix B ® vaccine, followed for an average time of 62 month (12-120 months). For each patient the following data were collected: age, serum albumin (sAlb), Blood urea nitrogen before HD session (BUN), age at vaccination, dialysis vintage, presence of systemic disease, type of vascular access, dialysis modality. Correlation between these factors and anti Hbs titer was estimated with multiple regression analysis. RESULTS: Anti-Hbs seroconversion rate ( Anti Hbs > 10 IU/l) was 77%. Better rate of seroconversion (86%) was observed in patients with arteriovenous fistula (AVF) and serum albumin > 3,5 g/dL (93%), while higher rate of not responders (50%) in patients with systemic diseases. The only parameter correlated to anti Hbs titer was sAlb (p =0,0012). sAlb was correlated to age in all patients (p=0,01) and age was correlated to higher anti Hbs titer in the responder group (p=0,018). DISCUSSION: In our experience an early vaccination, when patients on chronic HD are younger and in better nutritional conditions, improves anti-HBV response.

Hypertension and kidneys: unraveling complex molecular mechanisms underlying hypertensive renal damage.

Kidney damage represents a frequent event in the course of hypertension, ranging from a benign to a malignant form of nephropathy depending on several factors, that is, individual susceptibility, degree of hypertension, type of etiology and underlying kidney disease. Multiple mechanisms are involved in determination of kidney glomerular, tubular and interstitial injuries in hypertension. The present review article discusses relevant contributory molecular mechanisms underpinning the promotion of hypertensive renal damage, such as the renin-angiotensin-aldosterone system (RAAS), oxidative stress, endothelial dysfunction, and genetic and epigenetic determinants. We highlighted major pathways involved in the progression of inflammation and fibrosis leading to glomerular sclerosis, tubular atrophy and interstitial fibrosis, thus providing a state of the art review of the pathogenetic background useful for a better understanding of current and future therapeutic strategies toward hypertensive nephropathy. An adequate control of high blood pressure, obtained through an appropriate therapeutic intervention, still represents the key strategy to achieve a satisfactory control of renal damage in hypertension. In this regard, we reviewed the impact of currently available antihypertensive pharmacological treatment on kidney damage, with particular regard to RAAS inhibitors. Notably, recent findings underscored the ability of the kidneys to regenerate and to repair tissue injuries through the differentiation of resident embryonic stem cells. Pharmacological modulation of the renal endogenous reparative process (that is, with angiotensin-converting enzyme inhibitors and AT1 angiotensin II receptor blockers), as well as future therapeutic strategies targeted to the renopoietic system, offers interesting perspectives for the management of hypertensive nephropathy.

[Focal segmental glomerulosclerosis with IgA deposits in a patient with ulcerative colitis]. / Glomerulosclerosi focale segmentale con depositi di IgA in un paziente con rettocolite ulcerosa.

BACKGROUND: Glomerular diseases are described in patients with active ulcerative colitis (UC). Likely drug-induced interstitial nephritis, and nephrotic syndrome due to minimal change disease, have been reported in a few patients with UC on treatment with mesalazine and sulfasalazine (5-ASA). We describe a 33 year-old patient with a 5-years history of UC who recently developed nephrotic syndrome associated with microscopic haematuria. Blood pressure and renal function were normal. The patient was on azathioprine (AZA), mesalazine and sulfasalazine during the last year for his colitis, with good control of bowel disease. Renal biopsy revealed a focal segmental glomerulosclerosis (FSGS) associated with mesangial IgA deposits; no signs of interstitial nephritis were found. 5-ASA was discontinued, AZA was reduced and a rapid remission of the nephrotic syndrome was observed after 6 weeks of steroid therapy (1 mg/kg/day per os) associated with ramipril 5 mg/day, with a follow-up of 9 months. CONCLUSIONS: To our knowledge this is the first report of UC and GSFS associated with IgA deposits. The occurrence of nephrotic syndrome during UC is suggestive of an association between UC and FSGS, but a possible role of mesalazine and /or sulfasalazine in its pathogenesis cannot be excluded. Mesangial IgA deposits could be an "occasional" further occurrence, considering the chronic inflammation of colonic mucosa and the altered immune response of patients with UC.

IgA nephropathy: multivariate statistical analysis aimed at predicting outcome.

BACKGROUND: Several risk factors of IgA nephropathy (IgAN) have been identified, but their importance in predicting outcome is still controversial. METHODS: We conducted a retrospective study on 119 patients (pts) with IgAN. All had a follow-up of over five years (mean 134+/-56 months). For each patient we recorded age, 24h proteinuria, hematuria, renal function (RF), arterial hypertension (AH) and histological features. Multivariate analysis was done for predictive purposes (segmentation, using Chi-squared Automatic Interaction Detection-CHAID). RESULTS: AH at the time of renal biopsy was the principal and independent predicting factor: 30/50 (60%) hypertensive pts had serum creatinine > or =1.5 mg/dL at the end of follow-up compared to 9/69 (13%) pts with normal blood pressure. Age was a further predictive parameter: 21/28 (75%) pts with AH and age over 39 years had reduced RF at the last examination. In this subgroup, 18/19 (95%) with evidence of tubulo-interstitial lesions showed a decline of RF. CONCLUSIONS: AH and age alone are significant prognostic factors; tubulo-interstitial lesions are an additional pointer to poor outcome in these pts. The algorithm obtained with segmentation analysis may be a guideline for prognosis in single patients with IgA nephropathy.

Chromium-51 ethylenediamine tetraacetic acid glomerular filtration rate: a better predictor than glomerular filtration rate calculated by the Cockcroft-Gault formula for renal involvement in systemic lupus erythematosus patients.

OBJECTIVE: To investigate whether the ethylenediamine tetraacetic acid (EDTA) glomerular filtration rate (GFR) is a better indicator of the degree of renal involvement than serum creatinine concentration or creatinine clearance calculated by the Cockroft-Gault formula. METHODS: We studied prospectively all systemic lupus erythematosus (SLE) patients with normal or borderline serum creatinine concentration (<110 micromol/l) and urinary sediment abnormalities and/or proteinuria in the last 2 yr. EDTA-GFR, serum creatinine concentration, calculated creatinine clearance (Cockroft-Gault formula) and 24-h urine protein were determined at the same time. Renal biopsies were performed in patients with low values of EDTA-GFR or significant proteinuria. RESULTS: Twenty-three patients were identified, of whom 22 were females. The average age of the patients was 31.6+/-8.2 yr. Biopsies were assigned to WHO classes as follows: class II, 1 patient; class III, 6 patients; class IV, 10 patients; class V, 6 patients. The average serum creatinine concentration, EDTA-GFR and calculated creatinine clearance were 79.8+/-mol/l, 74.5 ml/min and 97 ml/min respectively. EDTA-GFR showed abnormal values (<80 ml/min) in 15 of the 23 patients (65.2%) while calculated creatinine clearance was abnormal (<80 ml/min) in three of the 23 patients (13%) (P<0.001). Using the Pearson correlation test, we did not find any correlation between EDTA-GFR or creatinine clearance values and the sum of activity and chronicity indices. CONCLUSION: GFR performed by EDTA-GFR correctly predicted renal involvement in SLE patients, whereas GFR calculated by the Cockcroft-Gault formula may have underestimated renal function. Significant numbers of patients with WHO class III, IV or V lupus nephritis may be missed if biochemical creatinine clearance or serum creatinine concentration alone is used to assess renal disease.

Lack of association between antiphospholipid antibody and WHO classification in lupus nephritis.

OBJECTIVE: To study the prevalence of antiphospholipid antibody (aPL) in patients with biopsy proven lupus nephritis (LN) and to investigate if there is any association between the presence of serum aPL and WHO classes. METHODS: Seventy-one patients (68 female and 3 male, mean age 31 years, range 10-67) meeting ACR criteria for the classification of SLE and with biopsy proven LN were included. For every patient, we evaluated anticardiolipin antibodies, lupus anticoagulant and renal biopsy classified according to the WHO classification criteria (activity and chronicity scores were included). Twenty-four hour urinary protein at the time of biopsy was considered. RESULTS: Twenty-nine patients had class V LN, 27 had class IV, 11 had class III, 3 had class II and 1 had class I. Twenty-seven (40.2%) patients were aPL positive. The prevalence of aPL positive patients was 45% in class V, 33.3% in class IV and 45.6% in class III. We did not find any significant association between the presence of aPL and the WHO class (p = 0.61 with class V, p = 0.31 with class IV and p = 0.73 with class III). There was no association between the presence of aPL and activity (p = 0.52) or chronicity scores (p = 0.42). We also did not find any association between proteinuria and the presence of aPL (p = 0.3). CONCLUSIONS: Our results suggest that there is no association between the presence of aPL and the different WHO classes. The presence of these antibodies does not seem to be related to histological activity or the chronicity of lupus nephritis nor proteinuria.

IgA nephropathy in cystic fibrosis.

The kidney does not usually present specific lesions in cystic fibrosis (CF), although in recent years renal involvement has been reported, particularly amyloidosis and immune complex glomerulonephritis. IgA nephropathy is rare. We report four cases of IgA nephropathy out of five renal biopsies performed in the last three years in patients with CF and renal involvement and discuss the possibility of a relationship between IgA nephropathy and CF.