R. Maiorca

Predictors of Renal and Patient Outcomes in Atheroembolic Renal Disease: A Prospective Study

Atheroembolic renal disease (AERD) is part of a multisystemic disease accompanied by high cardiovascular comorbidity and mortality. Interrelationships between traditional risk factors for atherosclerosis, vascular comorbidities, precipitating factors, and markers of clinical severity of the disease in determining outcome remain poorly understood. Patients with AERD presenting to a single center between 1996 and 2002 were followed-up with prospective collection of clinical and biochemical data. The major outcomes included end-stage renal disease (ESRD) and death. Ninety-five patients were identified (81 male). AERD was iatrogenic in 87%. Mean age was 71.4 yr. Twenty-three patients (24%) developed ESRD; 36 patients (37.9%) died. Cox regression analysis showed that significant independent predictors of ESRD were long-standing hypertension (hazard ratio [HR] = 1.1; P < 0.001) and preexisting chronic renal impairment (HR = 2.12; P = 0.02); use of statins was independently associated with decreased risk of ESRD (HR = 0.02; P = 0.003). Age (HR = 1.09; P = 0.009), diabetes (HR = 2.55; P = 0.034), and ESRD (HR = 2.21; P = 0.029) were independent risk factors for patient mortality; male gender was independently associated with decreased risk of death (HR = 0.27; P = 0.007). Cardiovascular comorbidities, precipitating factors, and clinical severity of AERD had no prognostic impact on renal and patient survival. It is concluded that AERD has a strong clinical impact on patient and renal survival. The study clearly shows the importance of preexisting chronic renal impairment in determining both renal and patient outcome, this latter being mediated by the development of ESRD. The protective effect of statins on the development of ESRD should be evaluated in a prospective study.

Identification of a New Locus for Medullary Cystic Disease, on Chromosome 16p12

Autosomal dominant medullary cystic disease (ADMCKD) is an interstitial nephropathy that has morphologic and clinical features similar to autosomal recessive nephronophthisis. The typical renal dysfunction associated with ADMCKD results mainly from a defect in urinary concentration ability, although results of urinalysis are normal. Recently, a locus on chromosome 1 was associated with ADMCKD, in DNA from two large Cypriot families, and genetic heterogeneity was inferred. We describe the genomewide linkage mapping of a new locus for medullary cystic disease, ADMCKD2, on chromosome 16p12 in a four-generation Italian pedigree. The family with ADMCKD2 fulfills the typical diagnostic criteria of ADMCKD, complicated by hyperuricemia and gouty arthritis. Marker D16S3036 shows a maximum two-point LOD score of 3.68, and the defined critical region spans 10.5 cM, between D16S500 and SCNN1B1-2. Candidate genes included in the critical region are discussed.

Association between Silica Exposure and Necrotizing Crescentic Glomerulonephritis with p-ANCA and anti-MPO Antibodies: A Hospital-Based Case-Control Study

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

Familial clustering of IgA nephropathy: Further evidence in an Italian population

Several lines of evidence suggest that genetic factors have an important role in the pathogenesis of immunoglobulin A (IgA) nephropathy. We report the prevalence of familial IgA nephropathy in a referral center in northern Italy and present the data on HLA genotypes in the families identified. Twenty-six of 185 patients (14%) with IgA nephropathy investigated in Brescia, Italy, were related to at least one other patient with the disease. Restriction fragment length polymorphism (RFLP) analysis of HLA-DR beta and HLA-DQ alpha and beta genes, as well as polymerase chain reaction-based oligonucleotide typing, was performed in family members. The 26 patients with IgA nephropathy belonged to 10 families. Familial relationships between the patients varied greatly, ranging from parent-child to sib-pair to more distant familial relationships. No common nephrotoxic factor was identified in the families. The intervals separating the apparent onset of disease in relatives with IgA nephropathy varied from 8 months to 13 years. In patients with a family history of IgA nephropathy, there was an increased incidence of HLA-DRB1*08 compared with those with sporadic IgA nephropathy. The study shows that a significant number of the patients with IgA nephropathy followed up in Brescia had a family history of disease. The fact that the Italian population, an ethnic group not previously examined, also presents an increased familial susceptibility to IgA nephropathy suggests that familial predisposition is a very common finding for IgA nephropathy. Thus, clinicians should become aware that IgA nephropathy may aggregate within families in a substantial number of cases. In addition, this subgroup of patients with IgA nephropathy offers an ideal opportunity to elucidate the molecular genetics of this disease.

A prospective comparison of bicarbonate dialysis, hemodiafiltration, and acetate-free biofiltration in the elderly

Hemodiafiltration (HDF) and more recently acetate-free biofiltration (AFB) have shown good blood purification and cardiovascular stability in young and middle-aged hemodialysis patients. It is not clear if this is also valid for elderly patients. Twelve patients aged more than 70 years (mean age +/- SD, 76 +/- 4 years) on regular dialysis for at least 5 months were treated with bicarbonate dialysis (BD), HDF, or AFB in a randomized sequence and prospectively followed for 6 months (72 dialysis sessions/patient) for each procedure. The dialysis solution (containing bicarbonate), blood flow rate, and dialysate flow rate were the same with all the methods. During HDF and AFB solutions containing bicarbonate at a concentration of 27 to 30 mEq/L and 145 mEq/L, respectively, were infused postdilution at a rate of 66 +/- 7 mL/min and 2.81 +/- 0.12 L/hr, respectively. During the period of observation we evaluated the number of intradialytic hypotensions, the episodes of nausea, vomiting, headache (dialysis intolerance), body weight, the interdialysis weight gain, the duration of the dialysis session, the number of hospitalizations/patient, and the length of hospitalization/patient. At the end of each observation period we determined: Kt/V, protein catabolic rate, acid base balance, serum creatinine, serum calcium, serum phosphorus, alkaline phosphatases, and serum intact parathyroid hormone. After the switch from BD to either HDF or AFB, the results have shown a significant reduction of dialysis hypotension episodes (18 percent on BD, 14 percent on HDF, and 13 percent on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.0001; and HDF v AFB, P = NS) and of dialysis intolerance (3.3 percent on BD, 1.3 percent on HDF, and 1.1 percent on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.019; and HDF v AFB, P = NS). Kt/V improved significantly after the switch from BD to either HDF or AFB (1.17 +/- 0.06 on BD, 1.32 +/- 0.12 on HDF, and 1.32 +/- 0.13 on AFB; BD v HDF, P = 0.021; BD v AFB, P = 0.003; HDF v AFB, P = NS). Protein catabolic rate also improved in HDF and AFB compared with BD (0.90 +/- 0.12 on BD, 1.03 +/- 0.15 on HDF, and 1.04 +/- 0.14 on AFB; BD v HDF, P = 0.001; BD v AFB, P = 0.009; and HDF v AFB, P = NS). AFB showed a better correction of acidosis compared either with BD or HDF (serum bicarbonate, 20.3 +/- 1.1 mEq/L on BD, 20.8 +/- 2.2 mEqL on HDF, and 22.2 +/- 2.4 mEq/L on AFB; BD v HDF, P = NS; BD v AFB, P = 0.01; and HDF v AFB, P = 0.030). The other parameters observed did not differ. In conclusion HDF and AFB show a better dialysis efficiency and a better hemodynamic tolerance compared with BD. This fact is associated with an improvement in protein intake as assessed by kinetic criteria. Acetate-free biofiltration has the further advantage of a better control of the acid-base balance compared with BD and HDF. HDF and AFB are useful dialytic options to traditional BD hemodialysis even in patients older than 70 years.

Direct Effect of the Correction of Acidosis on Plasma Parathyroid Hormone Concentrations, Calcium and Phosphate in Hemodialysis Patients: A Prospective Study

Background: Metabolic acidosis contributes to renal osteodystrophy and together with hyperphosphatemia, hypocalcemia and altered vitamin D metabolism may result in increased levels of intact parathyroid hormone (iPTH) and metastatic calcifications. However, the impact of the correction of metabolic acidosis on iPTH levels and calcium-phosphate metabolism is still controversial. Study Design: The effects of the correction of metabolic acidosis on serum concentrations of iPTH, calcium (Ca), phosphate (PO4) and alkaline phosphatase were prospectively studied. Twelve uremic patients on maintenance hemodialysis (HD) for 49 months (median; range 6–243 months) with serum bicarbonate levels ≤20 mmol/l were studied before and after 3 months of oral sodium bicarbonate supplementation. Predialysis serum bicarbonate, arterial pH, ionized calcium, plasma sodium, plasma potassium, serum creatinine, hemoglobin, Kt/V, postdialysis body weight, predialysis systolic and diastolic blood pressure were also evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3 ± 0.6 to 24.4 ± 1.2 mmol/l (p < 0.0001) and 7.34 ± 0.03 to 7.40 ± 0.02 (p < 0.001). iPTH levels decreased significantly from 399 ± 475 to 305 ± 353 pg/ml (p = 0.026). No changes in total serum Ca, plasma PO4, serum akaline phosphatase, Kt/V, serum creatinine, hemoglobin, body weight, predialysis systolic and diastolic blood pressures were observed. iCa decreased significantly. Conclusions: Our study demonstrates that the correction of metabolic acidosis in chronic HD patients reduces iPTH concentrations in HD patients with secondary hyperparathyroidism possibly by a direct effect on iPTH secretion.

Blood volume changes during three different profiles of dialysate sodium variation with similar intradialytic sodium balances in chronic hemodialyzed patients

The aim of this study was to evaluate the effects on blood volume (BV) preservation of three different profiles of dialysate sodium variation with similar intradialytic sodium balances. Ten uremic patients aged 50 +/- 11 years receiving regular bicarbonate hemodialysis for 49 +/- 57 months were studied. Each patient underwent three hemodialysis treatments with different modalities of dialysate sodium profiles: constant sodium hemodialysis (CHD), high-low sodium hemodialysis (H-LHD), and low-high sodium hemodialysis (L-HHD). In CHD, the dialysate sodium concentration was 141 mEq/L and did not change during treatment. In H-LHD and L-HHD, the dialysate sodium concentration at the start of dialysis was 160 mEq/L and 133 mEq/L, respectively, and remained constant for 60 minutes. At this time, a single-step break point of variation of dialysate sodium concentration occurred. The dialysate sodium concentration changed according to a model aimed to keep identical the amount of dialysate sodium exchanged in the three different dialysis procedures. The duration of hemodialysis, the blood flow rate, the dialysate flow rate, and the dialysis membrane were the same for all three different hemodialysis modalities. The ultrafiltration rate was kept constant during treatment. Total dialysate collection and intradialytic sodium balance were calculated for each hemodialysis session. Blood pressure and heart rate were monitored at 10-minute intervals; percent reductions of BV (%R-BV) were continuously monitored by an online optical reflection method (Hemoscan; Hospal-Dasco, Medolla, Italy). The results have shown a lower intradialytic %R-BV with H-LHD compared with L-HHD and CHD. No differences in total ultrafiltration rate, systolic and diastolic blood pressures, and heart rate were observed among the three different dialysis procedures. The total dialysate sodium collected and the intradialytic sodium balances were very similar among the three different dialysis procedures, confirming the accuracy of the precision of the sodium model used. The H-LHD sodium profile may be a useful tool in the prevention of excessive %R-BV and of dialysis intolerance episodes.

A prospective randomized trial on azathioprine addition to cyclosporine versus cyclosporine monotherapy at steroid withdrawal, 6 months after renal transplantation

BACKGROUND Many attempts have been made to withdraw steroid therapy in renal transplant patients in order to avoid its many side effects. Results have been, so far, controversial. In this randomized prospective study, we compare the efficacy of azathioprine adjuncts to cyclosporine at the time of steroid withdrawal, 6 months after transplantation, versus Cyclosporine monotherapy, in preventing acute rejection. METHODS One hundred and sixteen kidney transplant patients with good and stable renal function (creatininemia <2 mg/dl) received, in the first 6 months, cyclosporine + steroid. They were then randomized into two groups (A and B), and steroid therapy was withdrawn over 2 months. Group A (58 patients) continued on cyclosporine monotherapy, whereas group B (58 patients) added azathioprine (1 mg/kg/day) at the beginning of randomization and continued on cyclosporine + azathioprine. In both groups, patients resumed steroid therapy at the first episode of acute rejection. Follow-up after randomization was 5.3+/-1.6 years. RESULTS After 5 years, the incidence of steroid resumption was 57% in group A and 29% in group B (P<0.02); of those, 68% and 88% of them were within 6 months from randomization. Anti-rejection therapy was always successful. Five-year patient and graft survival rates were 90% and 88% in group A and 100% and 91% in group B. Creatininemia did not differ, at follow-up. Side effects differed only for mild and reversible leukopenia caused by azathioprine in group B. CONCLUSION Cyclosporine plus azathioprine is more effective than cyclosporine monotherapy in reducing the incidence of acute rejection after steroid withdrawal. Graft loss as a result of chronic rejection, mild in both groups, did not differ. Steroid withdrawal is feasible and advantageous, and the addition of azathioprine allowed 71% of our selected patients to remain steroid-free.

Outcome of peritoneal dialysis: comparative studies

Since the introduction of Continuous Ambulatory Peritoneal Dialysis (CAPD) nephrologists have been questioning the ability of the method to achieve the same results as hemodialysis (HD). Unfortunately, clinical and ethical considerations, including the right of patients to select their preferred dialysis treatment, make such an evaluation impossible in prospective, randomized studies. Hence, comparisons can be made only for series with differing case-mix which have been only occasionally and partially corrected for pretreatment differences by sophisticated statistical analysis. Moreover, the results are greatly affected by differences in experience with the two methods: the shorter existence of CAPD pays the price of all limited experiences, in terms of number of patients and duration of treatment. CAPD technique is still insufficiently standardized, with important differences in different centers in incidence of peritonitis and in catheter-related complications that greatly affect results.

Lipid peroxidation in normal pregnancy and preeclampsia.

Increased levels of lipid peroxidation may contribute to the development of endothelial injury which is a key pathogenetic factor in preeclampsia1. Moreover, lipid peroxides per se inhibit prostacyclin formation without affecting thromboxane synthetic pathways2. In this way they could directly contribute to the generation of the thromboxaneprostacyclin imbalance reported in preeclampsia. Increased blood levels of lipid peroxidation products in preeclampsia have been reported by many authors2–4. Levels of lipid peroxidation were usually determined as malondialdehyde (MDA) content measured by the TBA-test.