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Biomedical subjects

C Ponticelli

Publications and source records attributed to C Ponticelli.

At least 109 records · Page 6Linked to original sources

No association of converting enzyme insertion/deletion polymorphism with immunoglobulin A glomerulonephritis.

It has been recently reported that in type 1 diabetes the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme gene is associated with the presence of diabetic nephropathy. Tissue angiotensin I-converting enzyme is determined by I/D polymorphism, and it has been speculated that in diabetes differences of local angiotensin II availability determine the risk of renal disease. Since angiotensin II is thought to play an important role in the evolution of renal disease in general, we tested whether genotype distribution of the I/D polymorphism is also different in patients with immunoglobulin A-glomerulonephritis (IgA-GN). Furthermore we compared IgA-GN patients with (1) stable renal function or (2) terminal renal failure to investigate a potential role of the I/D polymorphism in the renal prognosis. We examined 122 patients with biopsy-confirmed IgA-GN who had stable renal function and 82 dialysis-dependent or transplanted patients with biopsy-confirmed IgA-GN. Furthermore, in 134 healthy individuals used as controls we analyzed the DNA for normal distribution of genotypes and allele frequencies. The polymorphic region was amplified using polymerase chain reaction with specific primers. Alleles were detected on 2% agarose gels. Genotype distributions and allele frequencies were not significantly different between controls and patients with IgA-GN and stable renal function. Furthermore, no significant difference in genotype distribution was detected between patients with IgA-GN and stable renal function compared with patients with IgA-GN and end-stage renal failure, although a trend for a higher frequency of DD-homozygotes was noted in the latter group (P = 0.07).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

High prevalence of a rare hepatitis C virus in patients treated in the same hemodialysis unit: evidence for nosocomial transmission of HCV.

Hepatitis C virus (HCV) is a major cause of hepatitis among patients treated with maintenance hemodialysis. Blood transfusion appears to be the primary risk factor, but nosocomial transmission of HCV in the dialytic environment has been hypothesized. We addressed this issue by analyzing the individual variation of genomic sequences of HCV in 28 patients on chronic hemodialysis (HD) from the same department and 25 environmentally unrelated patients with HCV-related liver disease. Genome variations of HCV were studied by single strand conformation polymorphism (SSCP) analysis of polymerase chain reaction products obtained from the 5'-untranslated region of the viral genome and by sequence analysis. Six different SSCP patterns were identified in HD patients versus 16 in control patients. Among HD patients the three more frequent SSCP patterns accounted for 85% of observations, while in the control group each pattern was found in 4 to 12% of patients. The ability of SSCP to discriminate sequence variation was proven by sequence analysis which confirmed identity/diversity of sequences selected by SSCP. Moreover, sequence analysis permitted a recognition of the most frequent genome observed in HD patients as a type 4 HCV, which is considered to be rare in the Italian population. The relative homogeneity of HCV variants in HD patients treated in the same HD and the high prevalence in this unit of a rare viral variant support the possibility of a nosocomial transmission of HCV in the dialytic environment.

Adult↗

A 10-year follow-up of a randomized study with methylprednisolone and chlorambucil in membranous nephropathy.

The natural course of idiopathic membranous nephropathy is variable, with some patients slowly progressing to renal failure while others maintain normal renal function over the entire time. Whether to treat this disease or not is controversial due to the lack of controlled data about the long-term effects of treatment. We updated at 10 years the results of a controlled trial in which 81 patients with idiopathic membraneous nephropathy and nephrotic syndrome were randomly assigned to receive symptomatic therapy (39 patients) or a treatment of six months with methylprednisolone and chlorambucil (42 patients). The probability of surviving without developing end-stage renal disease at 10 years was 92% in patients given methylprednisolone and chlorambucil versus 60% in controls (P = 0.0038). The slope of the reciprocal of plasma creatinine up to 10 years was significantly better in treated patients than in controls (P = 0.035). The probability of having a complete or partial remission of the nephrotic syndrome was significantly higher in treated patients (P = 0.000). Patients assigned to therapy spent significantly longer time without nephrotic syndrome than untreated patients (P = 0.0001). Four patients had to stop treatment because of reversible side-effects. In the long-term one treated patient developed diabetes and another one became obese. In conclusion, a six-month therapy with methylprednisolone and chlorambucil increases the probability of remission of proteinuria and protects from renal function deterioration even in the long-term. This treatment may avoid dialysis or death within 10 years to about one third of nephrotic patients with membranous nephropathy.

Adult↗

Cuff-shaving procedure. A rescue treatment for exit-site infection unresponsive to medical therapy.

We performed 41 cuff-shaving procedures in 38 patients on continuous ambulatory peritoneal dialysis (CAPD) with exit-site infection unresponsive to medical treatment. Cuff shaving was performed on three patients with two catheters each. This procedure was effective in eliminating 50% of S. aureus exit-site infection and all S. epidermidis exit-site infection, but was ineffective in Gram-negative exit-site infection. After cuff-shaving procedure, 20 catheters (49%) were removed; 11 for persistent tunnel infection and nine because of development of secondary peritonitis. The probability of catheter survival at 1 year was 50% and remained stable thereafter. Cuff-shaving procedure may be a valuable mode of therapy for treating patients with S. aureus and/or S. epidermidis exit-site infection unresponsive to medical treatment.

Anti-Bacterial Agents↗

Porokeratosis and immunosuppression.

Immunosuppression may favour the development of disseminated superficial porokeratosis (DSP). We report the clinical features and the outcome of DSP in 24 patients receiving immunosuppressive treatment (group A), and compare the characteristics of the disease with those of 13 immunocompetent patients with DSP (group B). The two groups were similar with regard to age, sex, area of skin involvement and mean follow-up. There was a family history of DSP in only two patients in group A, compared with five patients in group B (P = 0.03). The skin type, based on the tanning response to sunlight, was not significantly different between the two groups. Two of the 24 patients in group A had high sun exposure, compared with five of the 13 patients in group B (P = 0.03). Moreover, 10 patients in group A and 11 in group B (P = 0.01) exhibited worsening of the disease after exposure to sunlight, usually during the summertime. These observations appear to support the hypothesis that sun exposure is not always essential for the development of porokeratosis in immunosuppressed patients. None of our patients developed skin cancer in porokeratotic lesions during the follow-up period.

Adult↗

Corticosteroids in kidney transplant recipients. Safety issues and timing of discontinuation.

Corticosteroids have played a key role in the immunosuppression of organ transplantation. Unfortunately, the extensive use of these agents has resulted in disabling and life-threatening adverse effects in many patients. The advent of concomitant corticosteroid/cyclosporin regimens has allowed a reduction in the dosages of steroids administered, yet steroid-induced morbidity is still a major problem in many cyclosporin-treated renal transplant patients. After favourable initial experiences with cyclosporin monotherapy, several attempts at steroid-free immunosuppression in renal transplant patients have been undertaken, either by not starting steroids after transplantation or by stopping steroids in patients with stable graft function. Most controlled and uncontrolled trials showed that with either strategy short term graft survival was similar with or without steroids, but acute rejection was more frequent in patients not taking steroids. The percentage of patients who could be maintained steroid-free ranged from 28 to 94%, and was higher in patients who stopped steroids later than in those never receiving them. Little information is available about long term follow-up of these patients. Some studies reported late attrition of renal function in patients not taking steroids, while others reported a favourable outcome even in the long term. Steroid-free immunosuppression is feasible in renal transplant patients, but it requires careful monitoring of renal function and cyclosporin dosage. This strategy is particularly indicated in patients at high risk of cardiovascular disease or steroid-related complications, and in children. Nevertheless, several issues need to be better elucidated by further studies, namely the long term outcome of steroid-free immunosuppression, the advantages and disadvantages of steroid avoidance versus steroid withdrawal, and the criteria for selecting patients.

Adrenal Cortex Hormones↗

Reversible acute renal failure from gross haematuria due to glomerulonephritis: not only in IgA nephropathy and not associated with intratubular obstruction.

Seven patients with acute renal failure due to gross haematuria caused by glomerulonephritis are described. Gross haematuria lasting 4-40 days led to acute impairment of renal function of variable severity (peak plasma creatinine 1.3-12 mg/dl) and duration. While partial recovery of renal function occurred in all patients within few days, complete remission was observed only some months later. Three patients had IgA nephropathy (2 the primary form and 1 nephritis secondary to Schönlein-Henoch purpura), two patients had acute postinfectious glomerulonephritis, and two others had focal necrotizing (pauci-immune) glomerulonephritis. The glomerular changes seen in the renal biopsy were not enough to explain per se the renal function impairment. Tubular changes, however, were severe and consisted of tubular necrosis, erythrocyte casts, erythrocyte phagocytosis by tubular cells, accompanied by interstitial damage (oedema, red-cell extravasation, and inflammatory infiltrates). Study of the renal biopsies by immunofluorescence revealed no retrodiffusion of Tamm-Horsfall protein into the glomerular Bowman's space, a sign of obstructed tubular flow in any case. It is concluded that acute renal failure due to gross haematuria in glomerulonephritic patients may not occur only in IgA nephropathy, as reported so far, and is not associated with intratubular obstruction.

Acute Kidney Injury↗

Renal disease and patient survival in light chain deposition disease.

We evaluated retrospectively the presenting clinical features, response to treatment and clinical course of 19 patients with LCDD, 11 of whom had multiple myeloma. At presentation, renal insufficiency was present in 18 patients and proteinuria in 16. Renal biopsy revealed typical LCDD in 16 patients, while in the remaining three LCDD was associated with other abnormal tissue deposits. Extrarenal signs were observed in 12 patients (63%), with the liver, heart and peripheral nerves being the most frequently involved organs. After diagnosis, 18 patients underwent therapy: 2 received steroids alone and 16 were treated with steroids and cytotoxic drugs; 7 patients also underwent plasma exchange. At the end of the first month of treatment renal function improved in 5 patients, worsened in 5 and remained unchanged in 8. All but 3 of the patients continued treatment beyond the first month: 7 patients developed end-stage renal disease, 5 an improvement and 4 a worsening in renal function. No effect on proteinuria was observed. Extrarenal symptoms developed in 4 previously unaffected patients and in 3 others they extended to more organs. Sixteen patients died: 12 during the first year of the follow-up, and 4 at 21st, 34th, 37th and 82nd month of observation. Five patients died from neoplastic cachexia, 4 from hypokinetic cardiopathy, 3 from hemorrhagic complications, 2 from pneumonia and one from unknown cause. Mean patient survival after presentation was 18.1 +/- 20.7 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Cardiologic abnormalities in patients with long-term lupus nephritis.

To assess the cardiological status of patients with long-term lupus nephritis we evaluated 30 patients (mean age 43 +/- 11 years) with lupus nephritis lasting from at least 10 years (mean 15 +/- 5 years). At the time of cardiological evaluation the mean plasma creatinine was 132.6 +/- 11.1 mumol/l and in 28 patients lupus had been quiescent for at least 3 years. Fourteen patients (46.6%) showed one or more cardiac abnormalities: 10 had valvular lesions (1 verrucous endocarditis, 9 thickening and stiffness of one or more valves)--4 patients had regional myocardial akinesis as a consequence of a previous cardiac infarct (one had valvular abnormalities too). One patient had pulmonary hypertension probably secondary to pulmonary vasculitis. No patient had pericarditis. These cardiac abnormalities proved to be statistically correlated with the number of ARA criteria (p = 0.045), the number of lupus flares (p = 0.004), the serum levels of cholesterol (p = 0.04) and of triglycerides (p = 0.025) as well as the duration of hypercholesterolemia (p = 0.005) and of hypertriglyceridemia (p = 0.007). In conclusion, in patients with long-term lupus nephritis cardiac lesions are frequent. The main lesions are non-verrucous valvulopathy (probably a consequence of healing verrucous endocarditis) and cardiac infarct (caused by an accelerated atherosclerosis). On the contrary cardiac lesions caused by active lupus as pericarditis, myocarditis and verrucous endocarditis are rare.

Adult↗

Soluble interleukin-2 receptor (sIL-2R) levels in renal transplantation: comparison between clinical and laboratory analysis.

Soluble interleukin-2 receptor levels (sIL-2R) were retrospectively evaluated in 43 consecutive kidney transplant recipients (22 males, 21 females), from day 0 up to 90 days after transplantation. 11 pts were on CsA only, 13 on CsA + MP and 19 on CsA + MP + Aza. All graft-worsening episodes were then retrospectively analyzed, either according to clinical criteria only, or taking into account sIL-2R levels. On clinical grounds, 50 rejections were observed: "a posteriori" 5 turned out to be either infections or non-immunological worsenings of graft function (prevalence of misdiagnosis in the rejection set: 5/50, 10%). Of the 8 infections, 2 were actually treated as rejections (margin of error: 2/8, 25%). CsA toxicity was correctly diagnosed in 2/4 episodes. The analysis based on sIL-2R levels increase confirmed the clinical diagnosis in 52/79 cases (66%). The prevalence of misdiagnosis was: 21.2% in rejection, 2/3 in CsA toxicity, while infections were overestimated in 60% of cases. Isolated sIL-2R level increase was not associated with rejection in 87.5% of cases, while an associated increase of IL-2R and plasma creatinine had a 5% chance of being wrong. SIL-2R levels increased before any rise in plasma creatinine in late rejections (28 +/- 21 days after transplantation), while they increased after the rise of plasma creatinine in early rejections (10 +/- 5 days) (p = 0.014). In the rejection set, sIL-2R had a sensitivity of 83.4%, a specificity of 80%, a positive predictive value of 50.2% and a negative predictive value of 95.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of gastric acid secretion on intestinal phosphate and calcium absorption in normal subjects.

BACKGROUND: Phosphate-induced hyperparathyroidism still represents an intriguing problem in dialysis patients. Postprandial hyperphosphataemia is considered to be the main stimulus to parathyroid hyperfunction, and therefore many efforts have focused on the use of phosphate binders to prevent phosphate absorption. METHODS: We investigated whether the pH-mediated gastric ionization of calcium phosphate dietary salts is necessary for its intestinal absorption. In eight normal subjects we measured 24-h urinary calcium phosphate excretion and the postprandial blood calcium phosphate profile after a meal containing 1 g of calcium and 2 g of phosphate salts in a crossover placebo-omeprazole study. On two occasions the subjects received either placebo or omeprazole 60 mg/day 2 days before and during the day test. RESULTS: Serum gastrin levels were measured as an indicator of achlorhydria and were 13.7 +/- 1 pg/ml after placebo and 30.4 +/- 4.7 after omeprazole (P < 0.003). Postprandial plasma phosphate profiles were not significantly different between the two studies (+36 +/- 8% after placebo and +24 +/- 8% after omeprazole, NS), while plasma calcium increased by +6.1 +/- 1% after placebo and decreased by -4.2 +/- 0.7% after omeprazole (P < 0.01). The 24-h urinary phosphate excretion was 1068 +/- 85 mg after placebo and 773 +/- 55 after omeprazole (P < 0.002), while the 24-h urinary calcium excretion was 360 +/- 21 after placebo and 238 +/- 15 after omeprazole (P < 0.0001). A negative relationship was observed between absolute changes in plasma gastrin and those in urinary calcium (P < 0.009) and phosphate (P < 0.05). CONCLUSIONS: The inhibition of gastric acid secretion by omeprazole significantly reduces both urinary phosphate and calcium excretion after an oral load. The behaviour of the postprandial calcium-phosphate plasma profile suggests that gastric acid inhibition is more effective in reducing calcium rather than phosphate dietary salts absorption in normal subjects.

Absorption↗

A randomized trial comparing triple-drug and double-drug therapy in renal transplantation. Analysis at 7 years.

This is the 7-year update of a randomized trial comparing triple (TT) and double (DT) immunosuppressive therapy in renal transplantation. At 7 years, patient survival rate was 85% in DT vs. 87% in TT (P = NS); graft survival rate was 73% in DT and 68% in TT (P = NS); pure graft survival was 86% in DT vs. 77% in TT (P = 0.096). The 7-year graft survival rate was 67% for cadaver graft recipients vs. 92% for living-related graft recipients (P = 0.044). No difference in the slopes of plasma creatinine between the two groups was observed. Ten DT and 13 TT patients changed their original therapy: statistical analysis, however, was carried out according to intention to treat. Both CsA levels and doses were significantly higher in DT than in TT group (P < 0.001) at any time point up to the 7th year. At univariate analysis, a living-related donor kidney (P = 0.044) and immediate recovery of renal function (P < 0.001) were the only two parameters associated with graft survival at 7 years. At multivariate analysis, only early graft function recovery was correlated with late graft survival (RR = 10.480). Thus, even in the longterm, there is no difference between DT and TT, either in patient or in graft survival: at the doses we used, TT had a lower prevalence of late side effects than DT, however, long-term pure graft survival was better, although not significantly, in DT than in TT. The possibility of a safe shift from one regimen to the other one makes the two treatments complementary rather than alternatives.

Adult↗

Therapy for idiopathic membranous nephropathy: tailoring the choice by decision analysis.

Two Italian controlled trials demonstrated that the difference in remission rates obtained with six months of methylprednisolone and chlorambucil (MP+Ch) compared to MP was smaller than MP+Ch versus symptomatic therapy in the treatment of idiopathic membranous nephropathy nephrotic syndrome (NS). A decision analysis was used to compare the three treatment strategies, assuming triple probabilities and costs for MP+Ch complications compared to MP, with no risk for supportive therapy, referring to an average 40-year-old patient and using the quality-adjusted life expectancy year (QALY) as the utility scale. With MP+Ch the difference in expected QALY was 7.2 years compared to supportive therapy, and 2.6 years compared to MP. To offset the longer survival obtained with MP+Ch versus MP, it was assumed that all patients treated with MP+Ch would undergo either fatal (5% vs. 0.3% with MP) or non-fatal complications (95% vs. 15% with MP). This threshold denotes a great stability of the inequality in the expected QALY. Consequently, treatment with MP or with MP+Ch is justified if their side effects are considered to be a suitable trade-off for a five or seven QALY, respectively, longer survival. Only an absurd increase in the death rate with MP+Ch could offset the difference.

Adolescent↗