Background Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key ...factor affecting prognosis. Methods Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. Results Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mκ IgMκ/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 μmol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. Conclusion Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.
OBJECTIVE: Chronic renal insufficiency and/or proteinuria in type 2 diabetes may stem from chronic renal diseases (CKD) other than classic diabetic nephropathy in more than one-third of patients. We ...interrogated urine proteomic profiles generated by surface-enhanced laser desorption/ionization-time of flight/mass spectrometry with the aim of isolating a set of biomarkers able to reliably identify biopsy-proven diabetic nephropathy and to establish a stringent correlation with the different patterns of renal injury. RESEARCH DESIGN AND METHODS: Ten micrograms of urine proteins from 190 subjects (20 healthy subjects, 20 normoalbuminuric, and 18 microalbuminuric diabetic patients and 132 patients with biopsy-proven nephropathy: 65 diabetic nephropathy, 10 diabetic with nondiabetic CKD nd-CKD, and 57 nondiabetic with CKD) were run using a CM10 ProteinChip array and analyzed by supervised learning methods (Classification and Regression Tree analysis). RESULTS: The classification model correctly identified 75% of patients with normoalbuminuria, 87.5% of those with microalbuminuria, and 87.5% of those with diabetic nephropathy when applied to a blinded testing set. Most importantly, it was able to reliably differentiate diabetic nephropathy from nd-CKD in both diabetic and nondiabetic patients. Among the best predictors of the classification model, we identified and validated two proteins, ubiquitin and β₂-microglobulin. CONCLUSIONS: Our data suggest the presence of a specific urine proteomic signature able to reliably identify type 2 diabetic patients with diabetic glomerulosclerosis.
Background:
We conducted a pilot trial to compare the effectiveness and safety of 2 different treatments in patients with membranous nephropathy and nephrotic syndrome.
Methods:
To validate the ...hypothesis that the 2 treatments were equivalent, patients with biopsy-proven membranous nephropathy and nephrotic syndrome were randomly assigned to methylprednisolone alternated with a cytotoxic drug every other month for 6 months (group A) or to intramuscular synthetic adrenocorticotropic hormone administered twice a week for 1 year (group B).
Results:
The primary outcome measure is cumulative number of remissions as a first event. Fifteen of 16 patients in group A and 14 of 16 patients in group B entered complete or partial remission as a first event. After a median follow-up of 24 months (interquartile range, 15 to 25 months), there were 4 complete remissions and 8 partial remissions in group A versus 8 complete remissions and 6 partial remissions in group B. Median proteinuria decreased from protein of 5.1 g/d (interquartile range, 4.0 to 7.3 g/d) to 2.1 g/d (interquartile range, 0.4 to 3.8 g/d;
P = 0.004) in group A and 6.0 g/d (interquartile range, 4.4 to 8.5 g/d) to 0.3 g/d (interquartile range, 0.2 to 1.9 g/d;
P = 0.049) in group B. Two patients from each group interrupted treatment because of side effects or inefficacy.
Conclusion:
Most nephrotic patients with membranous nephropathy responded to either treatment. Proteinuria was significantly decreased with both methylprednisolone and cytotoxic agents or prolonged administration of synthetic adrenocorticotropic hormone, without significant differences between these 2 therapies.
Background:
Fabry disease is a lysosomal storage disease resulting from deficient α-galactosidase A (α-Gal A) activity. End-stage renal disease generally occurs around the fourth decade of age, and ...dialysis therapy is a life-saving procedure. For patients with Fabry disease undergoing dialysis, death usually occurs from cardiac or cerebrovascular complications. Recently, enzyme replacement therapy was introduced for treatment of the disease.
Methods:
We report results of several clinical outcomes after 2 years of treatment with α-Gal A in patients with Fabry disease undergoing dialysis. Nine dialysis patients underwent a complete clinical, cardiac, and cerebrovascular evaluation at baseline and after 24 months of treatment. Two patients reported a recurrent pain crisis, and 6 patients reported gastrointestinal symptoms. In all patients, enzyme replacement therapy was undertaken because of the presence of Fabry cardiomyopathy. A complete echocardiographic study was performed in 6 patients 12 and 24 months before and 12 and 24 months during enzyme replacement therapy.
Results:
Enzyme replacement therapy was well tolerated. Pain crises disappeared completely after approximately 6 months of treatment, and patients with gastrointestinal involvement reported improvement in symptoms after 6 to 8 months. At baseline, all patients had left ventricular concentric hypertrophy. Enzyme replacement therapy did not affect heart rate or mean arterial pressure. The mean slope of left ventricular mass index progression decreased from 0.98 ± 0.01 in the pretreatment period (24 months) to 0.46 ± 0.960 in the enzyme-replacement-therapy period (
P = 0.06).
Conclusion:
Our observation indicates that in dialysis patients, enzyme replacement therapy is safe and effective, improving global quality of life and possibly ameliorating the progression of typical Fabry cardiomyopathy.
Oral anticoagulation therapy (OAT) is the choice treatment for thromboembolism prevention in atrial fibrillation (AF), although data about OAT use in haemodialysis (HD) patients with AF are ...contradictory.
The effect of OAT on the risk of mortality, stroke and bleeding was prospectively evaluated in a population of HD patients with AF. All the patients of 10 HD Italian centres alive on 31 October 2010 with documented AF episode(s) were recruited and followed-up for 2 years. OAT and antiplatelet intake, age, dialytic age, comorbidities and percentage time in the target international normalized ratio (INR) range (target therapeutic range; TTR) were considered as predictors of hazard of death, thromboembolic and bleeding events.
At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (4 strokes, 3 haemorrhagic and 1 thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality (HR 1.71, CI 1.10-2.64, P = 0.02). The estimated survival of patients always taking OAT tended to be higher than that of patients who stopped taking (68.6 versus 49.6%, P = 0.07). OAT was not correlated to a significant decreased risk of thromboembolic events (HR 0.12, CI 0.00-3.59, P = 0.20), while it was associated with an increased risk of bleeding (HR 3.96, CI 1.15-13.68, P = 0.03). Higher TTR was associated with a reduced bleeding risk (HR 0.09, CI 0.01-0.76, P = 0.03), while previous haemorrhagic events were associated with higher haemorrhagic risk (HR 2.17, CI 1.09-4.35, P = 0.03).
In our population of HD patients with AF, the mortality is very high. OAT is not associated with increased mortality, while antiplatelet drugs are. OAT seems, on the contrary, associated with a better survival; however, it does not decrease the incidence of ischaemic stroke, whereas it increases the incidence of bleeding. Bleeding risk is lower in subjects in whom the INR is kept within the therapeutic range.
A randomized trial of cyclosporine in steroid-resistant idiopathic nephrotic syndrome. To compare the efficacy (induction of remission) and safety of cyclosporine (CsA) with those of supportive ...therapy in patients with steroid-resistant idiopathic nephrotic syndrome (INS), we organized an open, prospective, randomized, multicentric, controlled study for parallel groups, stratified for adults and children. Forty-five patients with steroid-resistant INS were randomly assigned to supportive therapy or CsA (5 mg/kg/day for adults, 6 mg/kg/day for children) for six months, then tapered off by 25% every two months until complete discontinuation. Four patients were lost to follow-up. During the first year 13/22 CsA-treated patients versus three of 19 controls attained remission of the nephrotic syndrome (P < 0.001). A symptom score was assessed at time 0 and at six months. The mean score significantly decreased in the CsA group (P < 0.001), but remained unchanged in the controls. At month 6 the mean urinary protein excretion, the mean serum proteins and plasma cholesterol had significantly improved in the CsA group but were not changed in the controls. There were no significant differences in serum creatinine and creatinine clearance between treatments (interaction time* treatments, P = 0.089 and P = 0.935, respectively) at month 6 versus basal. The CsA-related side-effects were mild; no significant difference in blood pressure between the two groups was seen at any time. This study shows that CsA can bring about remission in some 60% of patients with steroid-resistant INS. In patients with normal renal function and without severe hypertension, CsA at the therapeutic scheme adopted did not produce severe renal or extrarenal toxicity.
Medium- and large-vessel vasculitides (MVV and LVV, respectively) comprise a heterogeneous group of disorders whose common denominator is the inflammatory involvement of vessels of medium and large ...size. This disease spectrum includes giant-cell arteritis and Takayasu’s arteritis, which typically affect the aorta and its main branches, and Kawasaki’s disease and polyarteritis nodosa, which involve medium-sized arteries. Chronic periaortitis, characterized by a perivascular fibro-inflammatory reaction affecting the abdominal aorta and the periaortic tissue, frequently has a systemic distribution, involving other segments of the aorta and its major branches, and could thus be included in this group. Unlike small-vessel vasculitides, MVV and LVV do not cause glomerulonephritis, although glomerular immune-mediated lesions and tubulo-interstitial nephritis occur with varying frequency. However, MVV and LVV can often involve the renal artery and its branches, causing a wide array of lesions that range from renal artery stenosis to intra-renal vasculitis causing renal ischaemia/infarction, microaneurysms and haemorrhage. This review focuses on renal involvement in MVV and LVV and underlines why renal abnormalities in these syndromes should not be overlooked.
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