Giorgio Punzo

Uric acid: bystander or culprit in hypertension and progressive renal disease?

In humans, uric acid is the main urinary metabolite of purines. Serum levels are higher compared with other mammalians. Uric acid is an antioxidant and perhaps helps to control blood pressure during a low Na+ diet through stimulation of the renin–angiotensin system. Serum uric acid is also considered a marker of tubular reabsorption and ‘effective’ circulating blood volume. Moreover, hyperuricemia seems to be a cofactor in Na+-sensitive hypertension, a marker and possibly itself responsible for microvascular damage through stimulation of the renin–angiotensin system, inhibition of endothelial nitric oxide, and proliferative effects on vascular smooth muscle. As fructose-rich diets increase uric acid levels, hyperuricemia may also play a role in the metabolic syndrome, triggering insulin resistance and hypertension. A number of studies on rats rendered hyperuricemic by administration of uricase inhibitors have recently confirmed induction of arterial hypertension and microvascular injury, particularly in the remnant kidney or in cyclosporine-induced renal fibrosis.

Right Ventricular Dysfunction in Patients with End-Stage Renal Disease

Background: While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function. Methods: We examined 220 subjects grouped as follows: healthy controls (n = 100), peritoneal dialysis (PD; n = 26), hemodialysis (HD) with radial arteriovenous fistula (AVF; n = 62), and HD with brachial AVF (n = 32). Echocardiography including tissue Doppler imaging (TDI) of the right ventricle was performed in all patients. Results: Pulmonary pressure values progressively rose from controls across the 3 dialysis groups (21.7 ± 6.8, 29.7 ± 6.7, 37.9 ± 6.7 and 40.8 ± 6.6 mm Hg, respectively; p < 0.001). TDI indices of right ventricular function were more impaired in HD patients, particularly in those with brachial AVF. RVD, assessed by TDI myocardial performance index, was higher in HD patients compared with PD patients (71.3 vs. 34.6%, p < 0.001). Moreover, the prevalence of RVD further increased in patients with brachial AVF compared with the radial access (90.6 vs. 61.3%, p < 0.001). Conclusions: Compared to DP, HD increases the risk of RVD, particularly in the presence of brachial AVF. TDI may detect early functional failure of the right ventricle in HD patients.

Relation between right and left ventricular function in patients undergoing chronic dialysis

Aims Occurrence of heart failure during dialysis treatment is associated with high mortality. However, mechanisms underlying left ventricular dysfunction (LVD) in these patients are still elusive. In patients undergoing haemodialysis, arteriovenous fistula (AVF) is associated with right ventricular dysfunction (RVD) and a further impairment is observed when AVF is brachial rather than radial. However, it is not known whether AVF-induced RVD is associated with an impaired left ventricular function. We studied the relation between right and left ventricular function in 120 patients undergoing either haemodialysis or peritoneal dialysis and 100 healthy age-matched controls. Methods Echocardiography including tissue Doppler imaging (TDI) was performed for both ventricles. Average myocardial performance index (MPI) of the right ventricle (RV MPI) was obtained with a multisegmental approach by using TDI. Results RVD was higher in haemodialysis than peritoneal dialysis patients and a further increase was observed in haemodialysis patients with brachial access. Interestingly, RV MPI inversely correlated with indices of both left ventricular contraction and relaxation and the association was even stronger in haemodialysis patients, particularly in those with brachial AVF. Of note, dialysis patients in the upper tertile of RV MPI showed the larger impairment of left ventricular function. Regression analyses showed that RV MPI was independently associated with reduced left ventricular function. By contrast, LVD did not significantly affect right ventricular performance in this setting. Conclusion AVF-induced RVD may contribute to LVD in dialysis patients. AVF plays a pivotal role in triggering LVD via right-to-left ventricular interdependence.

Incremental Peritoneal Dialysis Favourably Compares with Hemodialysis as a Bridge to Renal Transplantation

Background. The value of incremental peritoneal dialysis (PD) as a bridge to renal transplantation (Tx) has not been specifically addressed. Methods. All consecutive Stage 5 CKD patients with at least 1 year predialysis followup, starting incremental PD or HD under our care and subsequently receiving their first renal Tx were included in this observational cohort study. Age, gender, BMI, underlying nephropathy, residual renal function (RRF) loss rate before dialysis and RRF at RRT start, comorbidity, RRT schedules and adequacy measures, dialysis-related morbidity, Tx waiting time, RRF at Tx, incidence of delayed graft function (DGF), in-hospital stay for Tx, serum creatinine at discharge and one year later were collected and compared between patients on incremental PD or HD before Tx. Results. Seventeen patients on incremental PD and 24 on HD received their first renal Tx during the study period. Age, underlying nephropathy, RRF loss rate in predialysis, RRF at the start of RRT and comorbidity did not differ significantly. While on dialysis, patients on PD had significantly lower epoetin requirements, serum phosphate, calciumxphosphate product and better RRF preservation. Delayed graft function (DGF) occurred in 12 patients (29%), 1 on incremental PD and 11 on HD. Serum creatinine at discharge and 1 year later was significantly higher in patients who had been on HD. Conclusions. In patients receiving their first renal Tx, previous incremental PD was associated with low morbidity, excellent preservation of RRF, easier attainment of adequacy targets and significantly better immediate and 1-year graft function than those observed in otherwise well-matched patients previously treated with HD.

Impact of dialysis modality on the appropriateness of left ventricular mass in patients with end-stage renal disease

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Focal segmental glomerulosclerosis as a complication of graft-versus-host disease.

Background. A 54-year-old man with multiple myeloma underwent peripheral blood stem cell transplantation (PBSCT) with cells donated by his human leukocyte antigen (HLA)-identical sister. Eight months after PBSCT, the patient experienced chronic graft-versus-host disease with skin involvement (generalized erythema), mucosal ulceration, sicca syndrome, and elevated liver enzymes. Two years after PBSCT, the patient developed nephrotic syndrome with massive proteinuria, which required hospitalization.Investigations. Physical examination, blood and urine analyses, liver function tests, 24 h urinary albumin excretion and renal biopsy.Diagnosis. Focal segmental glomerulosclerosis as a complication of graft-versus-host disease.Management. Prednisone, ciclosporin and an angiotensin-converting-enzyme inhibitor.

Early Treatment of Benign Prostatic Hyperplasia Implications for Reducing the Risk of Permanent Bladder Damage

A significant change has occurred in the management of symptomatic benign prostatic hyperplasia (BPH) since effective pharmacological treatment became available and led to a significant decrease in the number of surgical procedures in many Western countries. The hypothesis of a causative role of benign prostatic enlargement and bladder outflow obstruction (BOO) in lower urinary tract symptoms (LUTS) was based on the association between prostate growth and symptoms of prostatism in elderly men and on the dramatic reduction of LUTS upon relief of obstruction. Careful investigation into the epidemiology of LUTS and BPH failed to confirm such an association and opened new perspectives in the pathophysiology of lower urinary tract dysfunction and symptoms.The observation that LUTS were equally distributed in male and female cohorts, when matched for age, moved attention away from the prostate and towards the urinary bladder and its aging-related disorders. When BPH surgery was developed, the management of the disease was aimed at preventing death from chronic renal failure, but the picture has changed and modern medical treatment is now aimed at improving the patient’s quality of life.The increasing size of elderly populations in the Western world and the consequent financial constraints of national healthcare systems have raised the question of when pharmacological treatment of symptomatic BPH should be initiated. Retrospective and prospective analysis of various BPH populations and clinical studies has clearly defined the capacity of pharmacological treatment to reduce the incidence of complications of BPH, such as acute urinary retention and the need for surgery, but the cost/benefit ratio is unclear. Notwithstanding the limitations inherent in the experimental models, there is evidence from various animal models, investigating the pathophysiology of the urinary bladder in the presence of outflow obstruction, to indicate that a cause and effect relationship between BOO and bladder decompensation has been established and to support the hypothesis that permanent bladder damage may occur when the obstruction is not relieved early enough. Preliminary experimental evidence also suggests that α1-adrenoceptor antagonists may have a role in reducing the damaging effects of BOO on the urinary bladder.At present, there is no evidence to support the need for early pharmacological treatment of symptomatic BPH with no BOO beyond the obvious target of improving the patient’s quality of life. The evidence for early treatment of BOO and the need to preserve bladder function is clear. Further experimental and clinical research is required to identify markers of early bladder damage and decompensation which can be used to select patients for early pharmacological treatment of BPH.

Preventive hemostasis for hemodialysis vascular access surgical reinterventions

Surgical reinterventions for treatment of complications or ligation of haemodialysis vascular access (VA), when performed in or below the mid/lower part of the upper arm, could benefit from the use of preventive haemostasis with an inflatable tourniquet. This technique offers several advantages, such as the reduced risk of bleeding and the increased accuracy of dissection allowing for a minimally invasive approach. The use of preventive haemostasis is safe, economical and time-saving. All the secondary procedures on VA that could benefit from its use are reviewed.

Creation of autogenous radial cephalic direct wrist access for hemodialysis in the elderly using microsurgery

Purpose Guidelines recommend autogenous radial-cephalic AV fistula (RCAVF) as the first choice for hemodialysis. Concern has been raised that this is not suitable in the elderly. We assessed the results of microsurgery for RCAVF creation comparatively in patients older and younger than 70 years. Methods We prospectively followed 126 patients for three years. After systematic clinical and ultrasound assessment, a RCAVF was created using a surgical microscope. Patency was assessed immediately, at one week, one month and one year. Outcomes were recorded and stratified into two groups: <70y and >70y. Results RCAVF was created in 75.4% and 70.8% of the <70y and >70y groups, respectively. Incidence of early failure was 11% (<70y) and 13% (>70y). Primary and secondary patency at one year was 67% and 84% (<70y) versus 63% and 80% (>70y). Conclusions Microsurgery enabled the creation of RCAVF in >70y with acceptable risk of failure and slight differences by comparison with <70y. Older age should not preclude RCAVF creation.

Reduction of Early Postoperative Morbidity in Cardiac Surgery Patients Treated With Continuous Veno–Venous Hemofiltration During Cardiopulmonary Bypass

Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response syndrome. The major clinical features of this include a reduction of pulmonary compliance and increased extracellular fluids, with increased pulmonary shunt fraction similar to acute respiratory distress syndrome, thus resulting in prolonged mechanical ventilation time (VAM) and intensive care unit length of stay (ICU STAY). We evaluated the feasibility of an intraoperatory cardiopulmonary bypass (CPB) circuit connected with a monitor for continuous veno-venous hemofiltration (CVVH) to ameliorate pulmonary function after open heart surgery reducing VAM and ICU STAY. Forty patients undergoing elective coronary artery bypass grafting were randomized at the time of surgery into a control group (20 patients who received standard cardiopulmonary bypass) and a study group (20 patients who received CVVH during cardiopulmonary bypass). The analysis of postoperative variables showed a significative reduction of VAM in treated group (CVVH group mean 3.55 h +/- 0.85, control group 5.8 h +/- 0.94, P < 0.001) and ICU STAY (CVVH group mean 29.5 h +/- 6.7, control group 40.5 h +/- 6.67, P < 0.001). In our experience, the use of intraoperatory CVVH during cardiopulmonary bypass is associated with lower early postoperative morbidity.