Bilateral Striatal Necrosis after Sydenham's Chorea in a 7-Year-Old Boy: A 2-Year Follow-Up.

Child bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous condition. An association with group A streptococcus (GAS) infection was previously reported in two cases of BSN in infancy and early childhood. We here report on a 7-year-old boy who developed chorea and dystonia 20 days after symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance imaging scans, obtained before, soon after the onset of the post-Sydenham symptoms, and 1 year later were consistent with an evolution from bilateral striatal microbleeding to necrosis, and consequently reduced basal ganglia volume and enlargement of the frontal horns. No support was found for other possible autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN. Prednisone treatment was instituted and continued for 1 year. Two years after the onset of the post-Sydenham symptoms, the child, although much improved, still has generalized dystonic-choreic movements. This case confirms and extends into school age, the link between GAS and BSN.

Polymyography in the diagnosis of childhood onset movement disorders.

UNLABELLED: We report on the results of a clinical and polymyographic retrospective study of 61 paediatric patients with tremor, dystonia and/or myoclonus. Aim of the study was to verify the contribution of polymyography in the classification of these movement disorders and in their aetiological definition. METHODS: The movement disorders were clinically classified by two experts, based on clinical and videotape recordings evaluation; all patients underwent standardized polymyographic evaluation; aetiological diagnosis was performed according to diagnostic protocols for dystonia, myoclonus, tremor and psychogenic movement disorders. The polymyographic features were summarized in five different patterns (dystonia, subcortical myoclonus, myoclonic dystonia, tremor, normal) and compared with the clinical classification and with aetiological diagnosis. RESULTS: In more than 70% of the patients the polymyographic features were in accordance with the clinical classification; in 31% the polymyographic features allowed to identify a clinically unclassified movement disorder and in 19.6% disclosed a not clinically evident associated movement disorder. The polymyographic study did not contribute to the aetiological diagnosis, but was useful in supporting the clinical diagnosis of psychogenic movement disorder.

Human polyomavirus BK in patients with lupus nephritis: clinical and histological correlations.

Polyomavirus BK (BKV) reactivation can occur in immunodeficient patients. Few studies on BKV infection in patients with systemic lupus erytematosus (SLE) nephritis are available. Aim of this study was to analyse the prevalence of BKV infection by quantifying viral load and to investigate the association with clinical and histological parameters indicating duration, type and activity of SLE.BKV-DNA was evaluated by polymerase chain reaction in serum (sBKV) and urine (uBKV) specimens from 40 patients with SLE nephritis and 29 healthy controls. Renal function, urinary activity, clinical index of SLE activity [SLE Disease Activity Index (SLEDAI) score], CD4+/CD8+ ratio, histological classes and duration of SLE nephritis were compared according to the BKV-DNA-positivity.sBKV was present in 15% of SLE patients and in 13.8% of controls; uBKV in 32% of SLE patients and in 17.2% of controls. There was no significant difference in terms of kidney function, urinary activity, SLEDAI score, presence of anti-dsDNA antibodies, CD4+/CD8+ ratio and BKV viremia and/viruria, as well as there was no significant correlation between SLEDAI score, anti-dsDNA antibodies titers and median viral load. Duration of nephropathy tended to be shorter in patients with BKV viremia and/or viruria; proteinuria/creatininuria ratio tended to be higher in patients with positive sBKV and uBKV. BKV-DNA-positivity tended to be more frequent in patients treated with an immunosuppressive agent versus those on steroid treatment. Reactivation of BKV infection can occur in patients with SLE, although prevalence data do not significantly differ from those obtained in the control group. The trend toward an association between BKV infection and degree of proteinuria and less duration of SLE nephritis could indicate a major susceptibility to develop BKV infection in more active phases of the disease. The role of BKV reactivation in terms of clinical parameters and histological pattern, as well as the role of therapeutic protocols in the onset of BKV reactivation and, conversely, the therapeutic implication of BKV reactivation in SLE patients remain to be defined and should be addressed in further studies on a larger number of patients.

Risk management of renal biopsy: 1387 cases over 30 years in a single centre.

BACKGROUND: Although renal biopsy is largely employed, even in old patients with systemic diseases, few clinical studies have addressed its risk management. We aimed to obtain a comprehensive assessment of safety/utility ratio of percutaneous renal biopsy. PATIENTS AND METHODS: Retrospective review of all the 1387 patients who consecutively underwent renal biopsy in a single centre over three decades (1973-2002) was made, with calculation of complications, multivariate logistical analyses to evaluate risk factors of complications, and rate of alteration of clinical hypotheses by pathological diagnosis. RESULTS: There were no deaths and five major complications, (0.36%). One nephrectomy (0.07%), two surgical revisions (0.1%) and two arterial-venous fistulae (0.1%). There were also 337 minor bleeding complications (24.2%) (16.4% gross haematuria and 7.8% clinically relevant haematomas needing at least prolonged bed rest). Multivariate analyses demonstrated that the risk for complications was significantly increased by systemic autoimmune diseases with odds ratio (OR) 2.06, 95% confidence interval (CI)=1.40-3.01, end-stage kidney/acute-tubular necrosis (OR 2.96, 95% CI=1.19-7.30), and prolonged bleeding time test (BTT) (OR 1.87, 95% CI=1.17-2.83). Among the 1288 cases in which a clinical hypothesis before renal biopsy was recorded, renal pathology changed previous diagnoses in 423/1,288 (32.8%) of cases. CONCLUSIONS: Risk assessment demonstrates that renal biopsy is a useful procedure with a low incidence of serious complications. Platelet function is the only modifiable factor significantly related to bleeding complications, suggesting the need for a more standardized alternative to the BTT. Platelet function should be evaluated to select low-risk patients for renal biopsy as 'a day case procedure', in order to build adequate risk management strategies.

[Treating lupus nephritis: guideline from the Italian Society of Nephrology]. / Terapia delle nefriti proliferative lupiche; confronto degli schemi di associazione di farmaci citotossici più steroide rispetto al solo steroide: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of lupus nephritis (LN) treatment is presented. METHODS: SR of RCT and RCT on different therapeutic options for LN were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: One SR of 25 RCT and 6 further RCT were available to address this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. In LN patients, combining cyclophosphamide (CyA) and steroids as induction therapy results in a reduced risk of serum creatinine doubling compared to steroids alone, although there is no evidence of significant survival advantage and risk of ovarian failure was demonstrated (evidence from SR). The association of azathioprine (Aza) and steroids significantly reduces the risk of all-cause mortality compared to steroids alone (evidence from SR). No significant survival advantages from the association of plasma exchange and CyA or Aza are proven (evidence from SR). No significant differences on renal and survival endpoints are demonstrated with different dosing of CyA (evidence from RCT). CONCLUSION: In LN patients available evidence supports the hypothesis that immunosuppressive agents reduce the risk of all-cause mortality and the risk of progressive renal disease. Further studies are necessary to test new immunosuppressive agents such as mycophenolate mofetil in severe LN patients.

[Haemoglobin targets for chronic kidney disease: guideline from the Italian Society of Nephrology]. / Target ottimale di emoglobina per l'insufficienza renale cronica: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. In the present guideline, evidence of optimal haemoglobin (Hb) target levels in chronic kidney disease (CKD), either for pre-dialysis, dialysis or renal transplanted patients, is presented. METHODS: SR of RCT and RCT on different Hb target levels in patients with CKD were identified, referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Four SR (19 RCT) were found addressing the point. Methodological quality of available trials was suboptimal. In CKD patients (non-dialysis patients) Hb targets of 11.3 g/dL should be preferred to Hb >13.5 g/dL (evidence from RCT). A Hb target of 11.0-11.5 g/dL should be preferred in CKD patients receiving dialysis treatment without significant cardiac disease, since no survival benefits has been showed with Hb >14 g/dL (evidence from RCT). The optimal Hb target in haemodialysis patients with severe cardiac disease should be 10.0-10.5 g/dL (evidence from SR). Increases in Hb target lev-els are associated with improved quality of life, although this was mainly noticed in observational studies and in few RCT often relying on unvalidated quality of life assessment scales. CONCLUSION: In CKD patients current available evidence supports the hypothesis that optimal Hb targets should be low to subnormal.

Dual effect of methylprednsolone pulses on apoptosis of peripheral leukocytes in patients with renal diseases.

It is well known that change in apoptosis may modulate the natural story of illness, and that many drugs may act through modulation of apoptosis, but the role of steroids in acting through apoptosis in different settings, including renal diseases, has still to be elucidated. We studied the in vivo effects of steroids by oral assumption (10 to 25 mg/deltacortene) or by intravenous pulses (300 to 1000 mg/dose) on apoptosis and cellular subsets of peripheral lymphocytes, by evaluating DNA-fragmentation and lymphocyte subsets in 79 subjects: 22 controls and 57 patients with various renal diseases (25 Lupus-GN, 19 membranous-GN (MGN), 6 rapidly progressive-GN (RPGN), 2 acute interstitial nephritis (AIN), 5 on chronic dialysis. Baseline apoptosis was present in 1/22 (4.5%) of controls, 3/25 (12%) SLE, 2/6 (33.3%) RPGN and 10/19 (52.6%) MGN. A significant decrease in CD3+CD8+ cell count and a significant increase of the CD3+CD4/CD3+CD8+ ratio were found in apoptosis-positive subjects. DNA fragmentation did not change after oral steroids, paralleling a 22 to 32% decrease in total lymphocytes. Following intravenous methylprednisolone pulses, a deeper drop of all lymphocyte subsets was observed, while DNA fragmentation turned from present to absent in 2 MGN, but not in 2 RPGN, and from absent to present in 1 ARF and 1 SLE, independently of the dosage. We demonstrated that the presence of apoptosis in renal diseases is associated with decreased CD3+CD8+ cell count. Furthermore, steroid intravenous pulses, besides inducing a profound decrease in lymphocyte subsets, do exert a dual effect on baseline leukocyte apoptosis, eventually leading to a reversal of baseline patterns, either turning from negative to positive or from positive to negative. Oral steroid therapy did not influence baseline apoptosis.

Analysis of red cell parameters on the Sysmex XE 2100 and ADVIA 120 in iron deficiency and in uraemic chronic disease.

OBJECTIVE: The percentage measurement of hypochromic red cells (HYPO) and reticulocyte haemoglobin content (CHr) using the ADVIA system has recently been validated as a useful tool in indicating iron deficiency, also in cases of chronic diseases such as renal failure. The aim of this study was to evaluate the extent to which the red cell parameters, RBC-Y and RET-Y, provided by Sysmex XE 2100, correlate with HYPO and CHr. MATERIAL AND METHODS: The laboratory markers of iron status were evaluated together with HYPO, CHr, RBC-Y and RET-Y in 92 healthy subjects (C), 42 iron-deficient patients (ID) and 88 uraemic patients receiving regular dialysis treatment (RDT). RESULTS: In ID patients, increased HYPO and decreased RBC-Y, CHr and RET-Y values, with no overlapping with reference values, were found and a significant correlation was present between ADVIA 120 and Sysmex indices (p<0.001 for each correlation). In RDT patients, HYPO median values were increased with a wide distribution of values (95 % reference range = 0.7-27.5 % and 0.7-22.6 % in men and women, respectively). In contrast, RBC-Y was normal/increased (95 % reference range = 169.4-191.1 and 168.7-190.5 in men and women, respectively), even though there was a significant correlation between them (p<0.001). CHr and RET-Y values were within the reference range; moreover, in these patients mean cell volume of red cells and of reticulocytes (MCV and MCVr) median values were increased. CONCLUSIONS: This study confirmed the validity of RBC-Y in the management of ID, but not in RDT, where the diagnostic power of RBC-Y as an index of cell hypochromia is limited owing to high MCV values.

[Guidelines on water and solutions for dialysis. Italian Society of Nephrology]. / Linee Guida su acque e soluzioni per dialisi.

The National Society of Nephrology has promoted the development of specific Italian Guidelines for dialysis fluids. Two previous national inquiries showed a wide variety in the type and frequency of both microbiological and chemical controls concerning dialysis water, reinforcing the need for specific standards and recommendations. An optimal water treatment system should include tap water pre-treatment and a double reverse osmosis process. Every component of the system, including the delivery of the treated water to the dialysis machines, should prevent microbiological contamination of the fluid. Regular chemical and microbiological tests and regular disinfection of the system are necessary. 1. Chemical quality (Table: see text). Treated tap water used to prepare dialysis fluid should be within European Pharmacopoeia limits at the water treatment system inlet and at the reverse osmosis outlet. In addition dialysate, concentrate and infusion fluids must comply with specific Pharmacopoeia limits. The physician in charge of the dialysis unit is advised to institute a multidisciplinary team to evaluate the requirement for added chemical controls in the presence of local hazards. 2. Microbiological quality (Table: see text). High microbiological purity of dialysis fluid--regularly verified--is a fundamental prerequisite for dialysis quality and every dialysis unit should aim as a matter of course to obtain "ultra-pure" dialysate (microbial count <0.1 UFC/mL, endotoxins <0.03 U/mL). On-line dialysate ultrafiltration and regular disinfection of dialysis machines greatly enhance microbiological purity. On-line dialysate reinfusion requires specific devices used according to corresponding instructions and to more frequent microbiological tests. Dialysis fluids for home dialysis should comply with the same chemical and bacteriological quality. The appendix reports the water treatment system's technical characteristics, sampling and analytical methods, monitoring time-tables, as well as the origin and effects of the main toxic substances. Suggestions and questions concerning these guidelines are welcome to nefrologia@sin-italy.org.

[Nephrologists and porphyrias]. / I nefrologi e le porfirie.

As usually occurs for rare diseases, the word "PORPHYRIA" often recalls a confused topic with shaded boundaries, presenting "bullous" skin lesions, rare opportunity of diagnosis in clinical practice, unknown pathogenesis, and almost absent therapeutic options. The goal of this review is to draw attention to this topic, as new diagnostic and therapeutic tools might change the natural history of this disease. Porphyrias are disorders resulting from abnormalities of porphyrin metabolism. Porphyrins are molecules made up of four pyrrol rings, which constitute haeme-proteins, including haemoglobin. Following the "trigger" enzyme delta-aminolevulinic acid (ALA) synthase, which is capable of condensing succynil CoA and glycine, seven additional enzymes are involved in the process that eventually leads to haeme biosynthesis. Porphyrias are the result of total or partial deficiencies in these seven enzymes involved in haeme synthesis. Usually, the final haeme product exerts a negative feed-back on its synthesis. The enzyme deficiency that occurs in porphyrias is responsible for reduced haeme production, which, in turn, allows the cascade to be stimulated by increased activity of the trigger enzyme, ALA-synthase (ALA-s). However, due to the subsequent enzyme defects, notwithstanding increased ALA-s activity, haeme synthesis is blunted and intermediate metabolites accumulate. Clinical manifestations depend on which step the enzymatic defect occurs: if enzymatic defects are in the initial steps of the metabolic cascade, early metabolic intermediates will accumulate [i.e. ALA and porphobilinogen (PBG)] responsible for attacks of neurological dysfunction; if the enzymatic defects are in the final steps, sunlight-induced cutaneous lesions (phtotosensitivity) due to porphyrin accumulation in the skin will develop. The seven major human porphyrias may be classified into "hepatic or erythropoietic porphyrias" depending on the organ/tissue where metabolic alterations are more evident, or "acute or chronic porphyrias" depending on the prevalence of clinical symptoms, if neurologic (acute) or cutaneous (chronic). Only a small number of people with inherited enzyme deficiency will develop overt clinical disease, mainly because of the role of acquired aggravating and precipitating factors, such as drugs, hormonal causes, infection, caloric restriction, alcohol. The biochemical diagnosis of porphyrias relies on the detection of the consequences of increased ALA-s activity in the liver: overproduction, accumulation and increased excretion of early (ALA, PBG) or late (porphyrins) intermediate compounds in plasma, faeces and urine. A major difficulty arises from the knowledge that such abnormalities may be completely absent during the remission phases of the disease. Only in very specialised Centres it is now possible to measure specific haeme synthesis enzyme defects, and to perform molecular diagnosis by DNA analysis. The true prevalence of the diseases is unknown, ranging from 1:500 to 1:50,000. Therapeutic strategies include withdrawal of all common precipitants (drug, alcohol, fasting, infection), use of opiates and chlorpromazine, carbohydrates (300-400 g/day) and infusion of human haemine. Genetic therapies are being studied for the future.

Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in patients on chronic dialysis.

BACKGROUND: The actual prevalence and the clinical relevance of gene mutations of HFE (which are linked to hemochromatosis) have not yet been established in patients on chronic dialysis. On the basis of theoretical premises, it could be hypothesized that these genetic determinants might influence the response to iron intake and the susceptibility for iron overload in patients in parenteral iron therapy. Furthermore, carriers for these mutations might be prone to develop sporadic porphyria cutanea tarda and cardiovascular events. METHODS: C282Y/H63D mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis, 98 in HD) and correlated with biochemical parameters of iron status (ferritin (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red cell size and hemoglobin content), erythropoietin (EPO) dosage, major cardiovascular events and C-reactive protein as marker of chronic inflammation, in patients without iron therapy and after i.v. iron supplementation (< or = 60 mg/week) and with the presence of biopsy-proven porphyria. RESULTS: C282Y heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two patients (1.5%) showed double heterozygosis. No differences in baseline serum FER and TSAT and the other biochemical and clinical parameters were found in patients bearing mutations alleles nor after continuous iron therapy at low dosages. However, the prevalence of patients capable of maintaining normal hemoglobin (Hb) level without EPO therapy is increased in the C282Y-mutated patients. Only 1 patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene mutations (H63D heterozygosis). CONCLUSION: C282Y/H63D HFE gene mutations do not seem to be related to major abnormalities in biochemical parameters of iron status in dialysis patients without iron therapy or after i.v. iron supplementation, granted that low dosages are employed. Obviously, as our patients were exposed to a relatively uniform iron regimen in our clinical center (< or = 60 mg/week), it is unclear if other dosing regimens will unmask clinically significant differences between the heterozygotes and normals. The fact that the C282Y-mutated patients more frequently maintain high Hb values without EPO is interesting as could suggest a better use of available iron for erythopoiesis, but needs to be confirmed in larger samples. No clear association is demonstrated with porphyria cutanea tarda and major cardiovascular events.

Silica and renal diseases: no longer a problem in the 21st century?

Silicosis and other occupational diseases are still important even in the most developed countries. In fact, at present, silica exposure may be a risk factor for human health not only for workers but also for consumers. Furthermore, this exposure is associated with many other different disorders besides pulmonary silicosis, such as progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, glomerulonephritis and vasculitis. The relationships between these silica-related diseases need to be clarified, but pathogenic responses to silica are likely to be mediated by interaction of silica particles with the immune system, mainly by activation of macrophages. As regards renal pathology, there is no single specific clinical or laboratory finding of silica-induced nephropathy: renal involvement may occur as a toxic effect or in a context of autoimmune disease, and silica damage may act as an additive factor on an existing, well-established renal disease. An occupational history must be obtained for all renal patients, checking particularly for exposure to silica, heavy metals, and solvents.