Successful Extracorporeal Blood Purification Therapy using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report.

Introduction: In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI. Case presentation: We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient's haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris® haemodiafilter set, in series with an adsorber device (CytoSorb®). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient's conditions still improved and renal function recovered. Conclusions: Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock.

Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study.

There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P = 0.032). eGFR improved on Everolimus and worsened in controls (between group difference + 25.6 ml/min/1.73 m2, 95% CI 10.5-40.7, P = 0.002). BKV replication declined in the Everolimus group alone (from 6.4 ± 0.8 to 3.6 ± 1.6 Log 10 genomic copies, P = 0.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P = 0.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P = 0.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P = 0.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients.

Low Protein Diets and Plant-Based Low Protein Diets: Do They Meet Protein Requirements of Patients with Chronic Kidney Disease?

A low protein diet (LPD) has historically been used to delay uremic symptoms and decrease nitrogen (N)-derived catabolic products in patients with chronic kidney disease (CKD). In recent years it has become evident that nutritional intervention is a necessary approach to prevent wasting and reduce CKD complications and disease progression. While a 0.6 g/kg, high biological value protein-based LPD has been used for years, recent observational studies suggest that plant-derived LPDs are a better approach to nutritional treatment of CKD. However, plant proteins are less anabolic than animal proteins and amino acids contained in plant proteins may be in part oxidized; thus, they may not completely be used for protein synthesis. In this review, we evaluate the role of LPDs and plant-based LPDs on maintaining skeletal muscle mass in patients with CKD and examine different nutritional approaches for improving the anabolic properties of plant proteins when used in protein-restricted diets.

[mTOR inhibitors in kidney transplantation].

A changing paradigm of treatment of kidney transplant recipients is a new, wider approach to immunosuppression, which should take into account both antiviral and anticancer effects, in addition to cardiovascular protection. Recent observations suggest that the early introduction of mammalian target of rapamycin inhibitors (mTORi) in association with low dose CNI may offer many of these effects. The present manuscript summarizes benefits and contraindications of combinations with mTORi in kidney transplant immunosuppressive strategies.

Regression of asymptomatic cardiomyopathy and clinical outcome of renal transplant recipients: a long-term prospective cohort study.

BACKGROUND: Asymptomatic left ventricular hypertrophy (LVH) is highly prevalent and associated with an adverse outcome in renal transplant recipients (RTRs). Nonetheless, there are currently no available studies analyzing the effect of LVH regression on solid clinical endpoints in these patients. METHODS: This study is the prospective observational extension of two randomized controlled trials aimed at assessing the effect of active intervention on post-transplant LVH in RTRs. We evaluated the incidence of a composite of death and any cardiovascular (CV) or renal event in 60 RTRs in whom LVH regression was observed and in 40 whose LVH remained unchanged or worsened. RESULTS: During an 8.4 ± 3.5-year follow-up, 8 deaths, 18 CV events and 6 renal events occurred in the entire cohort. Multivariable analysis showed that age [hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.03-1.12 each 1 year, P = 0.002] and LVH regression (HR 0.42, 95% CI 0.22-0.87, P = 0.019) were significant predictors of the composite endpoint. Kaplan-Meier estimates showed better survival rates in patients in whom actual LVH regression was achieved (P < 0.001, log-rank test). Age (HR 1.09, 95% CI 1.03-1.15 each 1 year, P = 0.004), better graft function (HR 0.95, 95% CI 0.91-0.99 each 1 mL/min/1.73 m(2) increase in estimated glomerular filtration rate, P = 0.03) and LVH regression (HR 0.41, 95% CI 0.22-0.79, P = 0.01) were significant predictors of the CV endpoint. Patients with a left ventricular mass index decrease also showed better cardiac event-free survival (P = 0.0022, log-rank test). CONCLUSIONS: This is the first study to demonstrate that LVH regression, regardless of the therapeutic strategy adopted to achieve it, portends better long-term clinical outcome in RTRs.

Adenine phosphoribosyltransferase (APRT) deficiency: a new genetic mutation with early recurrent renal stone disease in kidney transplantation.

Adenine phosphoribosyltransferase (APRT) deficiency, a rare inborn error inherited as an autosomic recessive trait, presents with 2,8-dihydroxyadenine (2,8-DHA) crystal nephropathy. We describe clinical, biochemical and molecular findings in a renal transplant recipient with renal failure, 2,8-DHA stones and no measurable erythrocyte APRT activity. Homozygous C > G substitution at -3 in the splicing site of exon 2 (IVS2 -3 c > g) was found in the APRT gene. The patient's asymptomatic brother was heterozygous for such mutation, and his APRT activity was 23% of controls. A splicing alteration leading to incorrect gene transcription and virtually absent APRT activity is seemingly associated with the newly identified mutation.

Association of arterial hypertension with renal target organ damage in kidney transplant recipients: the predictive role of ambulatory blood pressure monitoring.

BACKGROUND: Although arterial hypertension is a powerful predictor of graft failure, only few studies have evaluated 24-hr blood pressure (BP) profile in renal transplant recipients (RTRs). METHODS: We performed ambulatory blood pressure monitoring (ABPM) in 94 RTRs (65 men; age 28-71 years) with 1-year functioning grafts. Serum biochemical parameters, daily proteinuria, and transplantation-related data were evaluated in all subjects. RESULTS: ABPM showed that only 5% of RTRs were normotensives (BP<130/80 mm Hg) and identified 29% of patients with nocturnal hypertension. A strong, direct correlation was shown between each set of both systolic BP and diastolic BP measured by ABPM and serum creatinine, daily proteinuria, and serum triglycerides (P at least <0.025 for each). Serum creatinine immediately after transplantation and 1-yr asleep diastolic BP were the only significant predictors of 1-yr creatinine (P<0.0001; r=0.49), whereas awake systolic BP was the only predictor of daily proteinuria (r=0.39; P=0.005) by multiple regression analysis. CONCLUSIONS: BP assessed by ABPM proved to be a stronger predictor of renal graft damage than traditional immunologic factors. ABPM improved the diagnostic accuracy of arterial hypertension in RTRs and was the only effective tool in disclosing the association of BP with 1-year renal transplant outcome.

Prevalence of fasting hypercalciuria associated with increased citraturia in the ambulatory evaluation of nephrolithiasis.

BACKGROUND: Nephrolithiasis is a common, high costing pathology of the urinary tract. The most common urinary abnormalities are fasting hypercalciuria, hypercalciuria and hypocitraturia. This study aimed to identify the principal urinary abnormalities in our patients. METHODS: Ninety-eight patients (pts) (43 females, 55 males) with recurrent calcium nephrolithiasis underwent metabolic evaluation. In two 24-hr urine collections the following parameters were evaluated: calcium, phosphate, sodium, potassium, chloride, magnesium, citrate, oxalate, uric acid, creatinine (Cr), urea, ammonium and pH; blood measurement of calcium, phosphate, sodium, potassium, chloride, magnesium, uric acid, Cr, urea, acid-base balance ionized calcium and intact parathyroid hormone (iPTH) were also performed. A first morning voided urine sample was collected for measuring the urinary cross-links and fasting calciuria. The tubular threshold of phosphate (TmP) was calculated according to Walton and Bijovet. Metabolic evaluation was repeated in 63/98 pts after 7 days on a low calcium diet. RESULTS: The most common urinary abnormalities were fasting hypercalciuria in 51/96 pts (53.1%), hypercalciuria in 33/97 pts (34%) and hypocitraturia in 29/98 pts (29%); 24/33 pts (73%) with hypercalciuria had fasting hypercalciuria. Hypercalciuria was partially corrected on the calcium-restricted diet, while fasting hypercalciuria was not. Urine citrate levels were significantly higher in patients with fasting hypercalciuria. CONCLUSIONS: Fasting hypercalciuria was the most frequent urinary abnormality and it was not corrected with a calcium-restricted diet. In fasting hypercalciuric patients, increased bone resorption activity could be responsible for higher citraturia levels.