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Purpose: Gut dysbiosis has been described in advanced, but not in initial stages of CKD. Considering the relevant impact of gut dysbiosis on renal and cardiovascular risk, its diagnosis and treatment are clinically relevant. Methods: We designed, open-label, placebo-controlled intervention study (ProbiotiCKD) to evaluate gut microbiota metabolism in a cohort of KDIGO CKD patients (n = 28) at baseline and after a randomly assigned treatment with probiotics or placebo. Gut microbiota status was evaluated on:. Results: Basal mean fecal Lactobacillales and Bifidobacteria concentrations were abnormally low in both groups, while urinary indican and 3-MI levels were, indicating a mixed (fermentative and putrefactive) dysbiosis. After treatment, mean fecal Lactobacillales and Bifidobacteria concentrations were increased, only in the probiotics group (p < 0.001). Conversely, mean urinary indican and 3-MI levels only in the group treated with probiotics (p < 0.001). Compared to placebo group, significant improvements of C-reactive protein (p < 0.001), iron (p < 0.001), ferritin (p < 0.001), transferrin saturation (p < 0.001), β2-microglobulin (p < 0.001), serum iPTH and serum calcium were observed only in the probiotics group. Conclusions: ProbiotiCKD is the first intervention study demonstrating that an intestinal mixed dysbiosis is present even in early CKD stage and can be effectively corrected by the novel mode of administration of high-quality probiotics with improvement of inflammatory indices, iron status and iPTH stabilization.

Purpose: The effects on renal prognosis of acute kidney injury after elective unilateral nephrectomy are ill-defined. We evaluated as whether post-operative acute kidney injury modifies renal outcome over the long term. Methods: This is a retrospective study examining all consecutive adult patients referred to three Nephrology Units and that had previously undergone elective unilateral nephrectomy. We evaluated the association of post-nephrectomy acute kidney injury with the combined renal outcome of chronic dialysis requirement, ≥ 40% decline in glomerular filtration rate or new-onset severe proteinuria (> 500 mg/24 h). Clinical correlates of acute kidney injury and renal outcome were also examined. Results: 106 patients were enrolled. 52 patients had post-operative acute kidney injury with a median increment of serum creatinine of 0.67 [0.48–0.86] mg/dl; in these patients, serum creatinine and urea increased from the first day post-nephrectomy while contraction of urinary output was found in 7 patients. Older age [OR: 1.72; 95% CI 1.05–2.82; P = 0.030] associated with post-operative acute kidney injury. Over a median follow-up of 8.9 [95% CI 3.1–24.2] years, the combined renal outcome occurred, respectively, in 28 (53.8%) and 14 (25.9%) patients with and without acute kidney injury (P = 0.003). Logistic regression analysis showed that acute kidney injury (OR: 3.22; 95% CI 1.35–7.66; P = 0.008) and male gender (OR: 2.72; 95% CI 1.08–6.85; P = 0.034) were associated with poor renal outcome after adjustment for main comorbidities. Conclusions: In our population of referred patients, acute kidney injury after unilateral nephrectomy was common and associated with progressive chronic kidney disease, especially in older males.

OBJECTIVES Kidney size has been found to be correlated with anthropometric features and kidney function. Therefore, we postulate that if the conventionally measured renal sonographic parameters (pole-to-pole length, width, and parenchymal thickness) are taken according to standardized rules and corrected for body height, their association with kidney function could be strengthened, thus helping validate renal sonographic information for a better assessment of chronic kidney disease (CKD) status. METHODS This cross-sectional study included 72 stable adult patients with stage 1 to 4 CKD. Sonographic parameters were obtained from both kidneys and averaged, and the measurements obtained were further corrected for patients' body height. The glomerular filtration rate (GFR) was estimated by the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS Parenchymal thickness and renal length showed the highest correlation level with the GFR. This significant correlation, however, was greatly ameliorated by the correction for patients' body height (r = 0.537; P < .001; r = 0.510; P < .001, respectively). Of note, the product of these two parameters corrected for body height showed the best degree of correlation with the GFR (r = 0.560; P < .001), as confirmed by analysis of variance after subdivision of the population into CKD stage groups according to the GFR. Receiver operating characteristic curve analysis for discrimination of a GFR of less than 60 mL/min indentified the combined parameter as the one with the highest area under the curve (0.78; 95% confidence interval, 0.66-0.89), followed renal length corrected for height (area under the curve, 0.77; 95% confidence interval, 0.66-0.88). CONCLUSIONS Correction of renal sonographic parameters for body height strengthens the degree of the correlation of renal sonography with the GFR. The improved correlation with the GFR makes renal sonography a reliable tool for a more complete assessment of patients with CKD.

Background: The antiproteinuric pharmacokinetics of Ramipril in response to different doses and modalities of administration has been poorly investigated so far. Study design: Prospective, open-label and not placebo controlled study. Setting and participants: 40 Caucasian adult patients having GFR≥50mL/min, proteinuria 1–3g/day; SBP/DBP≤150/90mmHg were recruited between June 2014 and November 2014. Factor and outcome: Impact on 24h proteinuria and fractioned proteinuria of Ramipril given at different dosages (2.5mg/day or Ramipril 5mg/day or Ramipril 10mg/day) and with different daily administration modalities (single or two divided doses) for cycles of 10days. Measurements: At the end of each cycle, 24h and fractioned proteinuria on three timed urinary collections (morning, afternoon and night) were measured. Results: Compared to baseline, Ramipril significantly reduced 24h proteinuria at each dose and modality of administration. In particular, the greatest effects were evident with the higher and divided dose of the drug. The analysis of the fractioned proteinuria showed that the greatest reduction was obtained in the night urinary collection by administering Ramipril 10mg/day in two divided doses. Limitations: Small sample size. Conclusions: Ramipril reduces proteinuria at any of the tested doses. Although the using of high and divided doses seems to maximize the antiproteinuric effect of the drug, possibly due to a better pharmacological coverage of the nocturnal period.

BACKGROUND: Ramipril administered once daily is characterized by an attenuation of its pharmacological activity in the following 24 hours, whose effects on antiproteinuric activity have not yet been investigated.METHODS: The antiproteinuric efficacy of Ramipril has been evaluated in a cross-over study in 20 patients with renal disease, proteinuria and hypertension (GFR50 mL / min, proteinuria

It is not known whether physical exercise increases daily proteinuria in patients with proteinuric nephropathies, thus accelerating progression of the renal lesion. This study evaluates the acute effects of physical exercise on proteinuria in young adults with immunoglobulin A (IgA) nephropathy.Changes induced by intense physical exercise on quantitative and qualitative proteinuria were evaluated in basal conditions and after 10 days of ramipril therapy in 10 patients with IgA nephropathy, normal glomerular filtration rate (GFR), proteinuria between 0.8 and 1.49 g/24 h, and "glomerular" microhematuria before and after the end of a maximal treadmill Bruce test (B-test). The basal study also was performed in 10 age- and sex-matched healthy volunteers.At rest, GFR averaged 141 +/- 23 mL/min; it increased by 16.3% +/- 3.3% (P0.005) and 7.1% +/- 1.6% at 60 and 120 minutes after the B-test, respectively. At rest, GFR-corrected proteinuria averaged protein of 0.76 +/- 0.21 mg/min/100 mL GFR; it increased to 1.55 +/- 0.28 mg/min/100 mL GFR after 60 minutes (P0.001) and declined to 0.60 +/- 0.11 mg/min/100 mL GFR at 120 minutes after the end of the B-test. The pattern of urinary proteins remained unchanged, as did microhematuria. Daily proteinuria was not different from the basal value on the day of the B-test. After ramipril therapy, patients showed a reduction in GFR, but no change in daily GFR-corrected proteinuria, pattern of urinary proteins, or hematuria.The increase in proteinuria after exercise in our patients is significant and is not prevented by ramipril therapy, but lasts less than 120 minutes. Therefore, it cannot modify daily proteinuria. Thus, these data do not support the need to reduce acute physical activity in patients with nonnephrotic renal diseases.

Early detection of progressive renal dysfunction in patients with coronary artery disease.BackgroundAn association between renal hemodynamic dysfunction and coronary artery disease (CAD) has been documented in chronic renal failure; however, no information is available in CAD patients with normal glomerular filtration rate (GFR). This study was aimed at evaluating early abnormalities and outcome of renal function in CAD patients.MethodsIn 15 nondiabetic patients with normal renal function and no significant stenoses in renal arteries, and having undergone coronary arteriography, we studied systemic and renal hemodynamics before and after a vasodilating stimulus induced by aminoacid (AA) infusion. A control group (C) consisted of 15 sex- and age-matched kidney donors. The statistical adequacy of the sample size was preliminarily verified. Renal clearances were repeated after two years.ResultsAt baseline, GFR (mL/min/1.73m2) averaged 81.4 ± 3.8 in CAD and 83.7 ± 1.4 in C (P = NS); RPF (mL/min/1.73m2) was 297 ± 22 in CAD and 456 ± 15 in C (P < 0.0001); filtration fraction was higher in CAD (P < 0.001). Plasma renin activity was higher in CAD (P < 0.005). The number of coronary stenoses was inversely correlated with RPF but not with GFR. In CAD, at variance with C, AA did not induce any increment of GFR, while RPF increased without achieving the unstimulated value of C. Blood pressure was comparable in CAD and C at baseline and not modified by AA. After two years, a significant decrease in GFR (-14%, P < 0.001) and RPF (-15%, P < 0.001) occurred only in CAD, and in either group, the response to AA did not differ from that detected at baseline.ConclusionIn CAD patients with normal GFR, reduction in renal perfusion and absence of renal functional reserve likely represent early markers of progressive renal dysfunction.

The possibility that the renal hemodynamic abnormalities associated with ciclosporin (CS) administration are enhanced in nephrotic patients (NP), leading to severe impairment of renal function and/or to modifications in proteinuria, has not hitherto been tested. Ten NP and 8 healthy subjects (NC) were examined before and after oral CS administration (10 mg/kg body weight in NP and 12 mg/kg body weight in NC: a lower dosage was adopted in NP because of edema overestimating the actual body weight) under water diuresis by standard renal clearance methods. Basal blood volume was lower in NP. Blood CS levels were not significantly different in the two groups. Basal glomerular filtration rate (GFR) was similar in NP and NC, while renal plasma flow (RPF) was lower in NP. After CS, both GFR and RPF significantly decreased in the two groups, but the percent decrease in inulin clearance was greater in NP. Filtration fraction increased only in NC. Basal renal vascular resistances were greater in NP, and significantly increased after CS in both groups. Basal fractional sodium excretion (FENa) was lower in NP: after CS FENa decreased only in NC. Neither plasma renin activity, nor plasma aldosterone changed after CS. When urinary protein excretion (UP) was corrected by GFR, no change was observed after CS; by contrast, selectivity of proteinuria (as assessed by the CIgG/CTransferrin ratio) markedly increased. Our data indicate that CS induces a greater fall in the GFR in hypovolemic NP than in healthy subjects, probably because in the former GFR becomes extremely plasma flow dependent.(ABSTRACT TRUNCATED AT 250 WORDS)