C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy

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ISOLATED SYSTOLIC HYPERTENSION CHARACTERISTICS: DATA FROM THE BRISIGHELLA HEART STUDY (ITALY) AND THE ENAH STUDY (CROATIA)

Objective: Isolated systolic hypertension (ISH) in elderly is associated with increased global risk. It could be considered as a rough biomarker of increased arterial stiffness and advanced biological aging. In our study, we evaluate the association between ISH and other cardio-metabolic risk factors in two rural European populations from South Europe (Italy and Croatia). Design and method: In this international prospective long-term follow up study data on 5162 subjects from BrEnah cohort formed from original cohorts of Brisighella Heart Study (Italy) and ENAH Study (Croatia) were analized. Out of them 2253 subjects (694 from Croatia, 1559 from Italy; 980m, 1273f) were eligible for further analyses. BP was measured using Omron 6 device following the ESH guidelines. Fasting blood was analysed for glucose, lipids, uric acid, serum creatinine. Results: Results In general rural population from South Europe prevalence of ISH is high. Difference between Croatian and Italian subgroups was found (28.8% vs. 44.8%; p<0.001; no gender differences) what is concordance with difference in age between two cohorts. Beside age, ISH was significantly associated with eGFR and various metabolic parameters including visceral obesity glucose intolerance and uric acid Conclusions: In this group of patients prevalence of ISH was high. Observed difference between Italian and Croatian subgroup is mostly due to difference in age. Metabolic disturbances are frequently associated with ISH additionally increasing global risk

METABOLIC SYNDROME IN EUROPEAN RURAL POPULATION-DATA FROM THE BRISGHELLA HEART STUDY (ITALY) AND ENAH STUDY (CROATIA)

Objective: Prevalence and characteristics of metabolic syndrome (MS) differ among various populations worldwide. This might explain the observed divergences in association of MS with cardiovascular (CV) and chronic kidney disease (CKD) outcomes. Our aim was to analyze differences in MS between two rural continental populations from South Europe (Italy and Croatia) and its association with CKD and hypertension (HT). Design and method: In this international prospective long-term follow up study data on 5162 subjects from BrEna cohort formed from original cohorts of Brisighella Heart Study (Italy) and ENAH study (Croatia) were analyzed. Out of them 1839 subjects (796 m, 1043 w) were eligible for further analyses, 848 from Croatian and 991 from Italian cohort. NCEP ATP III defi nition was used for MS diagnosis, CKD was defi ned as eGFR < 60 ml/min, and HT as BP > = 140/90 mmHg and/or taking antihypertensive drugs. Results: Overall prevalence of MS in the whole group was 32% without differences between Croatian and Italian subgroups (32.8% vs. 31.4%; p = 0.55). In Croatian group MS was more frequently present in women (35.7% vs. 27.2%; p = 0.01), while this was not found in Italian group (32.8% vs. 30.0%).Signifi cant differences were observed in prevalence of pathological values of fasting blood glucose, triglycerides, HDL-cholesterol, waist circumference and blood pressure (52.2 vs. 40.2; 71.9 vs. 64.3; 34.2 vs. 69.9; 93.2 vs. 72.0; 89.9 vs. 95.8, respectively, all p < 0.05).We failed to observe difference in the number (3,4 or 5) of diagnostic elements for MS between the two groups (p > 0.05). There was no difference in prevalence of HT (84.9 vs. 86.3%, p = 0.62). However, CKD was signifi cantly more prevalent in Italian cohort (23.5% vs. 20.5%;p = 0.001). HT was signifi cantly more prevalent in MS than in non-MS group, while we failed to fi nd difference in CKD. Conclusions: Although prevalence of MS was the same in two European rural region, significant differences in characteristics of MS were observed between Croatian and Italian subgroups. Observed differences could be explained more with lifestyle and tradition than genetic variations. Characteristics of MS should be separately analyzed in each population and results should be implemented in national programs and strategies for CKD prevention

Interferon Therapy for HCV-Associated Glomerulonephritis: Meta-Analysis of Controlled Trials

A relationship between hepatitis C virus (HCV) infection and chronic glomerulonephritis (GN) has been asserted on the grounds of epidemiological and experimental data. Although this suggests a role for an antiviral approach to HCV-associated GN instead of the more conventional immunosuppressive (or supportive) therapy, the optimal management of HCV related glomerulonephritis remains controversial. To compare antiviral with immunosuppressive therapy for HCV-associated GN. Meta-analysis of controlled clinical trials (CCTs) of the two treatments (antiviral versus immunosuppressive) of HCV-associated GN. We used the fixed or random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. The rate of proteinuria and serum creatinine decrease after therapy for HCV-associated GN were regarded as the most reliable outcome end-points. We identified six studies involving 145 unique patients with HCV-associated GN. Pooling of study results demonstrated that proteinuria decreased more commonly after IFN than corticosteroid therapy (OR 1.92 (95% CI, 0.39; 9.57), NS), P-test for heterogeneity, 0.06 (I2=52.9%). In a sensitivity analysis including only CCTs using standard IFN-doses, OR was 3.86 (95% CI, 1.44; 10.33, (P=0.007)), P-test for heterogeneity, 0.18 (I2=35.9%). No improvement of serum creatinine after IFN compared to immunosuppressive therapy was noted (OR, 0.59 (95% CI, 0.21; 1.65), NS), P-test for heterogeneity, 0.76 (I2=0%). Only three CCTs gave information on the rate of proteinuria decrease over follow-up (OR, 5.08 (95% CI, 0.69; 37.31), NS). A few major side effects were noted after IFN administration. Our meta-analysis indicates that standard IFN-doses were more effective than immunosuppressive therapy in lowering proteinuria of patients with HCV-related glomerulonephritis. However, no significant improvement in serum creatinine was seen by IFN or steroid therapy across the studies. Also, information on proteinuria recurrence after the completion of antiviral therapy was not sufficient. Prospective, randomized trials based on combined antiviral therapy (pegylated IFN plus ribavirin) with adequate dose and follow-up are required to assess the efficacy and safety of antiviral treatment of HCV-associated glomerulonephritis

Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors

BACKGROUND: Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial. METHODS: Patients with chronic kidney disease who were receiving RAAS inhibitors and who had serum potassium levels of 5.1 to less than 6.5 mmol per liter received patiromer (at an initial dose of 4.2 g or 8.4 g twice a day) for 4 weeks (initial treatment phase); the primary efficacy end point was the mean change in the serum potassium level from baseline to week 4. Eligible patients at the end of week 4 (those with a baseline potassium level of 5.5 to <6.5 mmol per liter in whom the level decreased to 3.8 to <5.1 mmol per liter) entered an 8-week randomized withdrawal phase in which they were randomly assigned to continue patiromer or switch to placebo; the primary efficacy end point was the between-group difference in the median change in the serum potassium level over the first 4 weeks of that phase. RESULTS: In the initial treatment phase, among 237 patients receiving patiromer who had at least one potassium measurement at a scheduled visit after day 3, the mean (±SE) change in the serum potassium level was -1.01±0.03 mmol per liter (P<0.001). At week 4, 76% (95% confidence interval, 70 to 81) of the patients had reached the target potassium level (3.8 to <5.1 mmol per liter). Subsequently, 107 patients were randomly assigned to patiromer (55 patients) or placebo (52 patients) for the randomized withdrawal phase. The median increase in the potassium level from baseline of that phase was greater with placebo than with patiromer (P<0.001); a recurrence of hyperkalemia (potassium level, ≥5.5 mmol per liter) occurred in 60% of the patients in the placebo group as compared with 15% in the patiromer group through week 8 (P<0.001). Mild-to-moderate constipation was the most common adverse event (in 11% of the patients); hypokalemia occurred in 3%. CONCLUSIONS: In patients with chronic kidney disease who were receiving RAAS inhibitors and who had hyperkalemia, patiromer treatment was associated with a decrease in serum potassium levels and, as compared with placebo, a reduction in the recurrence of hyperkalemi

Differences in Comorbidity Burden Between those with Chronic Kidney Disease and Normal Renal Function

Introduction and Aims: Chronic kidney disease (CKD) and renal replacement therapy are both associated with significant mortality and morbidity. Co-existing comorbidity is common. The degree to which the increased morbidity and mortality is a result of the CKD, and how much a result of the co-existing comorbidity is less clear. We aimed to describe the range of comorbidity at baseline in a population cohort containing all identified within a healthcare region with CKD, those on RRT and a sample of 20,000 individuals from the same population with normal renal function. Methods: The GLOMMS-II cohort contained all individuals with a low eGFR (<60) ml/min/1.73m2 measured in our healthcare region in 2003 (in 2/3 of these with “CKD” the low eGFR was present for at least 90 days, in 1/3 with “impaired eGFR” it was not present for at least 90 days); all those with raised PCR and ACR; all those receiving RRT and a 20,000 sample of those with only normal eGFR measurements in 2003. Data-linkage to hospital episode statistics in the five years prior gave information on comorbidity in 2003. The prevalence of common comorbidities in the subgroups of the cohort is described. The odds of having each comorbidity at baseline with adjustment for age and sex are presented. Results: The prevalence of most comorbidities was higher in those with more advanced CKD (including RRT, as table). After correction for age and sex, vascular comorbidity, diabetes and haematological malignancy continued to be strongly associated with more advanced CKD. The association for other comorbidities was less marked, particularly for dementia. Impaired eGFR was also associated with many of these comorbidities Conclusions: More advanced CKD was strongly associated with vascular comorbidity and diabetes even after correction for age. This association may in part be due to the role of these comorbidities in the aetiology of CKD, as well as a consequence. In the assessment of outcomes in CKD, the effect of these comorbidities on outcome over and above that of CKD itself should be investigated further