Ciro Esposito

Stimulation of Hepatocyte Growth Factor in Human Acute Renal Failure

Hepatocyte growth factor (HGF) is a potent mitogen for tubular cells. Experimental injury to the kidney is associated with HGF release both locally and by distant organs stimulated by circulating ‘injurins’. In this study, the serum HGF concentration was measured in patients with acute renal failure (ARF). Normal subjects and chronic renal failure patients either not on dialysis or on regular dialysis treatment served as controls. Human mesangial cells were incubated with sera from ARF patients and controls. The serum HGF concentration was strikingly increased in ARF patients (478 ± 68 ng/dl) and was normal in chronic renal failure patients not on dialysis (20 ± 3 ng/dl) and in those on regular dialysis treatment (25 ± 3 ng/dl). Serum of ARF patients strongly stimulated HGF release from mesangial cells (1,384 ± 55 ng/ml) in comparison with normal serum (67 ± 10 ng/ml). These results indicate that in ARF HGF participates in tubular repair both as an endocrine factor, released in the circulation, and as a paracrine substance, diffusing to the tubules from the mesangium.

Risk Factors for Chronic Renal Dysfunction in Lung Transplant Recipients

Several factors predispose to renal dysfunction (RD), a common complication of solid organ transplants. We evaluated the impact of clinical and laboratory parameters on the decline of renal function in lung and heart-lung transplant recipients. We enrolled 45 patients who survived more than 6 months after transplantation, had normal renal function and urinalysis before the surgery. The prognostic value of variables for the occurrence of RD was calculated by univariate analysis. Thirty patients developed RD, defined as doubling of serum creatinine or creatinine steadily >1.5 mg/dL after a median time of 12 months. Serum creatinine above 0.9 mg/dL during the month preceding lung transplant, systolic blood pressure above 130 mmHg, and pretransplant idiopathic pulmonary hypertension were significantly associated with the development of RD. Our findings indicate that increased systolic blood pressure, reduced glomerular filtration rate, and idiopathic pulmonary hypertension are risk factors for chronic RD in lung transplant recipients.

Hyperkalemia-induced ECG abnormalities in patients with reduced renal function.

Hyperkalemia is a potentially lethal condition to be aware of in the presence of ECG abnormalities especially in patients with reduced renal function. However, ECG abnormalities are not always dependent on the degree ofhyperkalemia but may be aggravated by the rapidity of the development of hyperkalemia and by associated electrolyte disorders. We describe 3 patients with renal failure and different ECG changes induced by hyperkalemia. More severe changes were observed when hyperkalemia developed rapidly, but not in presence of electrolyte disorders. Even minor ECG abnormalities must alarm physicians in patients with renal failure since severe hyperkalemia is not always associated with critical ECG changes.

Saquinavir in steroid-dependent and -resistant nephrotic syndrome: a pilot study

BACKGROUNDnSome difficult cases of idiopathic nephrotic syndrome (NS) have been treated with a HIV protease inhibitor provided with proteasome-inhibiting activity. The objective of this study was to limit nuclear factor κB (NF-κB) activation which is up-regulated in these patients, aiming at decreasing proteinuria and prednisone need.nnnMETHODSnTen cases with long-lasting (up to 15 years) history of NS with steroid dependence (six cases, of which three with secondary steroid resistance) or resistance to steroids (four cases) unsuccessfully treated with multiple immunosuppressive drugs, accepted a treatment with the protease inhibitor saquinavir. p50/p65 NF-κB nuclear localization and immunoproteasome/proteasome messenger RNA (mRNA) were monitored in peripheral blood mononuclear cells (PBMCs). The effects of saquinavir on NF-κB nuclear localization in cultured PBMCs and in immortalized human podocytes were assessed.nnnRESULTSnAfter a median follow-up of 14.7 months (6-68.7), 1/4 primary steroid-resistant NS (SRNS) and 5/6 steroid-dependent NS or secondary SRNS became infrequent (5) or frequent (1) relapsers, with 63% prednisone reduction (from 25.3 to 8.4 mg/kg/month, P = 0.015). Saquinavir was effective in association with low doses of calcineurin inhibitors (cyclosporine 2 mg/kg/day or tacrolimus 0.01-0.06 mg/kg/day). No side effects were observed apart from transitory mild diarrhoea. In PBMCs, NF-κB was down-regulated, while MECL-1 immunoproteasome/beta2 proteasome mRNA ratio was reversed to normal values. In culture, saquinavir blunted NF-κB activation in human podocytes and in PBMCs.nnnCONCLUSIONSnIn this pilot study, a HIV antiprotease drug reduced proteinuria and had a steroid-sparing effect in some multidrug-resistant/-dependent NS. This observation warrants further investigation.

Microalbuminuria and sRAGE in High-Risk Hypertensive Patients Treated with Nifedipine/Telmisartan Combination Treatment: A Substudy of TALENT

Some antihypertensive drugs have also renoprotective and anti-inflammatory properties that go beyond their effect on blood pressure. It has been suggested that microalbuminuria and glomerular filtration rate (GFR) are associated with circulating levels of the soluble form of the receptor, sRAGE (soluble receptor for advanced glycation ends-products). In the present analysis, we used data from the TALENT study to evaluate soluble receptor for advanced glycation end-products (sRAGE) plasma levels in patients with hypertension and high-cardiovascular risk-treated nifedipine and telmisartan in combination. Treatment with nifedipine-telmisartan significantly decreased mean systolic and diastolic ambulatory blood pressure and resulted in a significant increase in sRAGE plasma concentrations after 24 weeks of therapy. We concluded that in hypertensive patients with early-stage renal disease, sRAGE concentrations are not influenced by either microalbuminuria or GFR. Long-term treatment with a combination of nifedipine-telmisartan may have a beneficial effect increasing sRAGE plasma levels, thus exerting an atheroprotective and anti-inflammatory activity.

Epidemiology of CKD regression in patients under nephrology care

Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60–15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m2/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18–24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting per se for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14–0.57; p<0.0001) while mortality risk did not differ from that in non-regressors (HR: 1.16; 95% CI 0.73–1.83; p = 0.540). Spline models showed that the reduction of ESRD risk associated with positive ΔGFR was attenuated in advanced CKD stage. CKD regression occurs in about one-fourth patients receiving renal care in nephrology units and correlates with low proteinuria, BP and the absence of PKD. This condition portends better renal prognosis, mostly in earlier CKD stages, with no excess risk for mortality.

Hemodialysis vascular access: everything you always wanted to know about it (but were afraid to ask).

Vascular accesses are essential for effective dialysis treatment. Arteriovenous fistulas, grafts and central venous catheters are the options available to the nephrologist, but they all have their pros and cons. All of the 3 types of vascular access share the same complications but at different rates, and their costs vary enormously, with on balance the arteriovenous fistula being the best choice. Nevertheless, recently the number of incident patients starting dialysis treatment with a venous catheter as vascular access has been steadily increasing. This is true even for more advanced countries such as the United States, where despite the efforts made to promote the use of fistulas, their prevalence is still low compared with Europe. Moreover, nowadays nephrologists are required to master technical skills that once were those of surgeons and to perform interventions to preserve the patency of the access. The aim of this paper is to review the prevalence, benefits and complications of the different vascular accesses in light of the most recent findings.

Relationship between sRAGE and eotaxin-3 with CRP in hypertensive patients at high cardiovascular risk.

BACKGROUNDnCardiovascular disease (CVD) is the leading cause of death in Western countries and is highly prevalent in patients with kidney disease. Traditional risk factors for CVD often accompany kidney dysfunction, and chronic kidney disease per se is considered an additional risk factor. Risk stratification for CVD remains suboptimal even after the introduction of global risk assessment by various scores. This has prompted the search for novel markers of cardiovascular risk, and several biomarkers have been suggested as candidates, together with C-reactive protein (CRP). The objective of the present study was to investigate the relationship between novel biomarkers of vascular inflammation (soluble form of the receptor for advanced glycation end products [sRAGE] and eotaxin-3) with CRP in a population of hypertensive patients at high cardiovascular risk.nnnMETHODSnPlasma sRAGE, high-sensitivity CRP (hs-CRP) and eotaxin-3 were measured in 399 hypertensive patients (265 men, mean age 58 ± 8 years)with diabetes mellitus, metabolic syndrome or organ damage.nnnRESULTSnPlasma concentrations of sRAGE, eotaxin-3 and hs-CRP were not different between diabetic and nondiabetic subjects. Univariate analysis showed that plasma levels of sRAGE and eotaxin-3 were not associated with hs-CRP in either subgroup.nnnCONCLUSIONnOur study confirms the robust and widely studied role of CRP as an important marker of vascular inflammation. We also postulate the possible involvement of sRAGE and eotaxin, 2 novel biomarkers, in CVDs. On the basis of our results, we can put forward the hypotheses that hs-CRP, s-RAGE and eotaxin are reliable but unrelated cardiovascular risk markers.

Inadequate Macronutrient and Micronutrient Intakes in Hemodialysis and Peritoneal Dialysis Patients: Data from a Seven-Day Weighed Dietary Record

Background/Aims: It is very important to assess the nutritional intake in patients on dialysis given the high prevalence of poor nutritional status of those in this population. The aim of this study was to assess nutrient intakes in hemodialysis (HD) and peritoneal dialysis (PD) patients. Methods: A clinical cross-sectional study was conducted over 7 days on 14 dialysis patients (98 days) who were trained to keep a weighed food record and a 7-day food diary. Nutrient intake adequacy was compared with specific guidelines for Italians and dialysis patients. Results: The mean daily protein intake (0.92 ± 0.36 g/kg) and energy intake (EI; 25.3 ± 7.4 kcal/kg) were inadequate according to the European best practice guidelines (EBPG). The ratio of EI to resting energy expenditure was 1.22. Inadequate intakes, compared to the EBPG, were found for calcium (525 ± 162 mg/day) and iron (8.7 ± 2.1 mg/day). Dietary fiber (14.7 ± 8.7 g/day), niacin (14.4 ± 5.2 mg/day), thiamine (0.8 ± 0.3 mg/day) and riboflavin (1.1 ± 0.4 mg/day) were also inadequate according to the Italian recommended dietary allowances (LARN). HD patients did not display different nutrient intakes between the dialysis days and the interdialytic period. Overall, the percentage of days during which nutrient recommendations were not satisfied ranged from 16 to 100% depending on the nutrient. Conclusion: Macronutrient and micronutrient intakes in HD and PD patients are largely inadequate compared to the EBPG. The weighed dietary record appears to be a useful and accurate tool for individual assessment of food intake in motivated patients. No nutrient intake differences were found between dialytic and interdialytic days in patients on HD.