Davide Rolla

Prolonged therapy with ACE inhibitors induces a regression of left ventricular hypertrophy of dialyzed uremic patients independently from hypotensive effects

Left ventricular hypertrophy (LVH), which frequently occurs in chronic uremia, may be due in part to factors other than arterial hypertension, chronic anemia, and/or other well-known loading conditions inherent to the uremic state. Angiotensin-converting enzyme (ACE) inhibitors may be able to reverse LVH by mechanisms independent of their antihypertensive effects. In this study, 18 subjects free of arterial hypertension or severe anemia were selected from 170 chronically hemodialyzed uremic patients after fulfilling the criterion of a supranormal left ventricular mass (LVM). Ten subjects agreed to undergo treatment with 2.5 to 20 mg lisinopril every other day over a period of 2 years, during which annual determinations of the LVM by echocardiography and of the 24-hour blood pressure with a portable device were carried out. Eight patients unwilling to undergo the treatment served as controls. The average resting left ventricular mass index (LVMi) of the overall group was 178 +/- 30 g/m2 body surface area (+/- SD), and did not differ between the two subgroups. Lisinopril treatment significantly decreased the LVM of eight of 10 treated subjects and actually even completely normalized it in three. The LVM of the untreated group remained unchanged. Systolic and diastolic blood pressures were 138 +/- 5 mm Hg and 78 +/- 6 mm Hg in the treated group and 133 +/- 9 mm Hg and 75 +/- 4 mm Hg in the untreated group, respectively (P = NS), and did not vary over the following 2 years. This study indicates that a mild degree of LVH, which is seemingly independent of arterial blood pressure load, does exist in a tight subset of uremic patients. This study also demonstrates that this type of LVH is apparently nonprogressive. ACE inhibitors given at doses not affecting blood pressure are able to reverse it.

Effects of ACE inhibitors on long-term outcome of renal transplant recipients: a randomized controlled trial.

Background Available data on the role of renin-angiotensin system blockade in renal transplantation are inconclusive. Herein, we report the long-term results of a randomized controlled trial planned to evaluate the impact of angiotensin-converting enzyme inhibitors (ACE-i) on the cardiovascular outcome of renal transplant recipients (RTRs) receiving calcineurin inhibitors, steroids, and mycophenolate mofetil. Methods Thirty-six RTRs were allocated to receive ACE-i and 34 served as controls. Survival free of a composite endpoint consisting of death, major cardiovascular events, renal graft loss or creatinine doubling, and survival free of each single endpoint were analyzed in both groups according to a modified intention-to-treat analysis. Results During a 10-year follow-up, three patients died (one in the ACE-i group and two controls) and three lost their graft (two receiving ACE-i and one control). Three major cardiovascular events were observed in the ACE-i group and 12 among controls (P=0.008). At the end of observation, a significant increase in urinary protein excretion rate was only observed in controls (P=0.017). Compared with controls, RTRs administered ACE-i had significantly better survival free of the combined endpoint (P=0.0102, log-rank test) and free of major cardiovascular events (P=0.0027) without significant differences in renal outcome. By Cox regression analysis, ACE-i therapy resulted in the most powerful predictor of survival free of composite endpoint (hazard ratio, 0.165; 95% confidence interval, 0.053–0.512; P=0.0018) and survival free of major cardiovascular events (hazard ratio, 0.209; 95% confidence interval, 0.068–0.636; P=0.0059). Conclusions Prolonged therapy with ACE-i was associated with better general and cardiovascular outcome of RTRs without detrimental effects on renal graft function.

Bone Disease in Long-term Renal Transplant Recipients with Severe Osteopenia: A Cross-sectional Study

Background. Fracture is a disabling clinical outcome after transplantation, but there is little histopathological information on long-term renal recipients with severe osteopenia. Methods. Twenty kidney recipients (8.3±1.9 years after transplantation), 13 males and 7 females (five postmenopausal) with nearly normal renal function, affected by severe osteopenia (T-score: males=−4.9±0.28; females= −5.08±0.47) underwent bone biopsy and morphometric X-ray absorptiometry to evaluate vertebral fractures. Results. Histopathological diagnosis was osteoporosis-osteopenia in seven patients, osteitis fibrosa in six, prevalent osteomalacic lesion in six, and “normal” bone in one patient. Significant increases in osteoid volume (OV/BV), osteoid surface, osteoblastic surface (ObS/BS) and osteoid thickness were observed. OV/BV and Obs/BS ratios were inversely correlated to cumulative doses of MPRED (r2=0.85 P<.0001 for both ratios), whereas age, sex, time after transplantation, iPTH levels, and cumulative cyclosporine A dose were not related to osteoblastic indices. Osteoclast surface was slightly increased. Widened mineralization lag times were observed, with normalcy of the bone formation rate. Half of the patients showed fractured vertebrae. No differences in T scores were found when patients were subdivided into groups “with” or “without” vertebral fractures. A higher prevalence of fractures was observed in patients with osteoporosis-osteopenia compared to other osteopathies (P<0.02). No relationships between bone volume versus T-scores were observed. Conclusions. In long-term renal transplant recipients, severe osteopenia does not predict osteoporosis alone. The main abnormality we found was an increase in osteoblastic activity with a slight mineralization defect. The heterogeneous bone illness we observed would suggest performing bone biopsy in these patients.

Cytokine mRNA expression in chronically rejected human renal allografts

Abstract:  Although both immunologic and non‐immunologic components may cause kidney allograft chronic rejection (KGCR), also referred to as chronic allograft nephropathy (CAN), its pathogenesis is largely not yet understood. To explore relevant immunologic mechanisms occurring in KGCR, we have analyzed in surgically removed KG the transcription of the following cytokine and apoptotic molecule genes: interleukin (IL)‐2, IL‐3, IL‐4, IL‐5, IL‐6, IL‐10, tumor necrosis factor (TNF)‐α, IFN‐γ, FAS, and FAS‐L. Semiquantitative RT‐PCR was used and KG explants were obtained from two groups of transplanted patients. Group 1 was represented by CR/CAN KG, removed for: (a) superimposed symptoms of acute lesions (SAL) due to tapering or suspension of immunosuppression (subgroup 1a, eight cases); (b) causes other than SAL (two cases, subgroup 1b). Group 2 comprised explanted kidneys with no CR/CAN (three cases – vascular thrombosis, intrarenal hemorrhage and vascular thrombosis). The results showed that in group 1 IL‐ 6 was detectable in seven of 10, IL‐10 in six of 10, IFN‐γ in five of 10, and IL‐3 in four of 10 cases with a variable pattern of reciprocal association. IL‐2 and TNF‐α were represented in one of 10 cases only. Particularly, in the subgroup 1b IL‐10 was never detected. Among the most represented cytokines of group 1, IL‐10 as well as IL‐3 were never found in group 2. The peculiar expression of IL‐10 and IL‐3 and partially IL‐6 seems to support the hypothesis that a Th2 pattern predominantly characterizes KGCR, thus indicating that Th2 cytokines, likely produced by different intragraft cell types including T cells, macrophages and natural killer (NK) cells, may represent an important component in the pathogenesis of this process. Moreover, IL‐10 seems to exquisitely characterize a group of CR/CAN kidney grafts more prone to immunologic assaults.

Ultrasound findings in dual kidney transplantation.

PurposeThis study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT).Materials and methodsWe reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55–82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function.ResultsThree patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (p<0.01) than SKTs.ConclusionsCDUS provides useful information in patients with DKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.RiassuntoObiettivoScopo del presente lavoro è stato analizzare gli aspetti eco-color Doppler (USD) in pazienti con trapianto di doppio rene (DKT) e paragonare volume renale e indice di resistenza (RI) nei pazienti con DKT e con trapianto di rene singolo da donatore ideale (SKT).Materiali e metodiAbbiamo valutato i dati clinici e di imaging [30 USD, 5 risonanze magnetiche (RM) e 1 tomografia computerizzata (TC)] in 30 pazienti con DKT (23 maschi e 7 femmine, età media 65 anni; range 55–82) paragonando volume renale e RI con quelli di 14 pazienti con SKT e livelli simili di funzione renale.RisultatiTre pazienti avevano disfunzione del trapianto: uno con rigetto cronico e due con patologie coinvolgenti un solo rene (1 pielonefrite incrostata rene sinistro e 1 occlusione dell’arteria renale sinistra). Alterazioni asintomatiche unilaterali sono state riscontrate in 6 ulteriori pazienti. Nei DKT asintomatici non sono state riscontrate differenze significative di lunghezza, volume, ecogenicità corticale e RI tra i due reni; nei DKT i reni erano più piccoli (volume 116,7 vs. 171,6 cc) e con RI più alto (0,76 vs. 0,68) (p<0,01) rispetto ai SKT.ConclusioniL’USD fornisce utili informazioni nei pazienti con DKT, permettendo il riscontro di anomalie asintomatiche unilaterali non clinicamente sospette; a livelli comparabili di funzione renale, i pazienti con DKT hanno valori di RI più alti e volume renale inferiore rispetto ai pazienti con SKT.

Pemetrexed-induced acute kidney failure following irreversible renal damage: two case reports and literature review

Background Pemetrexed (PEM) is a new-generation multitargeted antifolate agent with a demonstrated broad-spectrum activity in several types of human cancers, including non-small cell lung cancer (NSCLC) and mesothelioma. Major side effects include dose-limiting hematologic toxicities. PEM nephrotoxicity is well known; however, its frequency is considered to be low. Case Presentation Here we report two cases of acute kidney injury (AKI) related to PEM administration (500 mg/m2) in patients with NSCLC. The first patient required hemodialysis treatment and was submitted to renal biopsy which showed acute tubular damage and interstitial edema without acute tubular necrosis. No other potential nephrotoxic agents were identified. The second patient developed AKI, not proven by biopsy and did not require renal replacement therapy. Both patients, on regular supplementation with folic acid and vitamin B12, concomitantly developed myelosuppression and even several months after PEM withdrawal, showed only a modest improvement of renal function. Conclusions PEM is an antifolate antineoplastic agent with a broad-spectrum activity in locally advanced or metastatic NSCLC. It has been shown that PEM allows longer survival. The risk of acute or chronic kidney disease may be one of the prices to be paid for this success.

De novo post-transplant thrombotic microangiopathy localized only to the graft in autosomal dominant polycystic kidney disease with thrombophilia

Introduction: Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation and is mostly related to the prothrombotic effect of calcineurin inhibitors (CNIs). A subset of TMA (29%-38%) is localized only to the graft. Case 1: A young woman suffering from autosomal dominant polycystic kidney disease (ADPKD) underwent kidney transplant. After 2 months, she showed slow renal deterioration (serum creatinine from 1.9 to 3.1 mg/dl), without hematological signs of hemolytic-uremic syndrome (HUS); only LDH enzyme transient increase was detected. Renal biopsy showed TMA: temporary withdraw of tacrolimus and plasmapheresis was performed. The renal function recovered (serum creatinine 1.9 mg/dl). From screening for thrombophilia, we found a mutation of the Leiden factor V gene. Case 2: A man affected by ADPKD underwent kidney transplantation, with delay graft function; first biopsy showed acute tubular necrosis, but a second biopsy revealed TMA, while no altered hematological parameters of HUS was detected. We observed only a slight increase of lactate dehydrogenase (LDH) levels. The tacrolimus was halved and plasmapheresis was performed: LDH levels normalized within 10 days and renal function improved (serum creatinine from 9 to 2.9 mg/dl). We found a mutation of the prothrombin gene. Only a renal biopsy clarifies the diagnosis of TMA, but it is necessary to pay attention to light increasing level of LDH. Conclusion: Prothrombotic effect of CNIs and mTOR inhibitor, mutation of genes encoding factor H or I, anticardiolipin antibodies, vascular rejection, cytomegalovirus infection are proposed to trigger TMA; we detected mutations of factor II and Leiden factor V, as facilitating conditions for TMA in patients affected by ADPKD.

Viabahn stent for hemodialysis shunt: efficacy, long segment recanalization and prognostic factors for reintervention

Introduction: The study evaluated the Heparin Bioactive Surface (HBS) Viabahn Stent (W.L. Gore & Associates, Flagstaff, Arizona) efficacy in the maintenance or re-establishment of hemodialysis. Materials and methods: Fifty HBS Viabahn stents deployed in 37 consecutive patients with hemodialysis dysfunction from January 2008 to May 2016 were evaluated in a single-institution retrospective review. Outcomes were stent patency intended as primary circuit patency (PP), assisted primary patency (APP), target lesion primary patency (TLPP) and secondary patency (SP). Moreover, the risk factor analysis for hemodialysis dysfunction that required reintervention was performed. A subgroup analysis was conducted to assess patency of Viabahn stent to treat peripheral venous long segment obstruction (LSO). Results: Overall Kaplan-Meyer PPs were 60% at 12 months and 42% at 24 months. Overall TLPP estimated rates were 68% and 49% at 12 and 24 months, respectively. The corresponding SP rates were 85% and 78% at the same period. Estimated PP rates at 12 and 24 months for stent placement after peripheral venous long segment recanalization procedure were 53% and 31%, respectively. Corresponding SP rates were 82% and 68%, respectively. The APP rates were 79% at 12 months and 61% at 24 months. Female sex, access age and thrombosis were associated with reduced primary patency. Conclusions: Considering the high rates of PP, TLPP, APP and SP, Viabahn stents have been proven effective in maintaining or re-establishing the hemodialysis access. Moreover, stent placement after recanalization of LSO of venous out-flow represented a valid approach to rescue a dysfunctional fistula that would otherwise be abandoned.

Valutazione eco-color Doppler nel doppio trapianto di rene

PurposeThis study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT).Materials and methodsWe reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55–82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function.ResultsThree patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (p<0.01) than SKTs.ConclusionsCDUS provides useful information in patients with DKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.RiassuntoObiettivoScopo del presente lavoro è stato analizzare gli aspetti eco-color Doppler (USD) in pazienti con trapianto di doppio rene (DKT) e paragonare volume renale e indice di resistenza (RI) nei pazienti con DKT e con trapianto di rene singolo da donatore ideale (SKT).Materiali e metodiAbbiamo valutato i dati clinici e di imaging [30 USD, 5 risonanze magnetiche (RM) e 1 tomografia computerizzata (TC)] in 30 pazienti con DKT (23 maschi e 7 femmine, età media 65 anni; range 55–82) paragonando volume renale e RI con quelli di 14 pazienti con SKT e livelli simili di funzione renale.RisultatiTre pazienti avevano disfunzione del trapianto: uno con rigetto cronico e due con patologie coinvolgenti un solo rene (1 pielonefrite incrostata rene sinistro e 1 occlusione dell’arteria renale sinistra). Alterazioni asintomatiche unilaterali sono state riscontrate in 6 ulteriori pazienti. Nei DKT asintomatici non sono state riscontrate differenze significative di lunghezza, volume, ecogenicità corticale e RI tra i due reni; nei DKT i reni erano più piccoli (volume 116,7 vs. 171,6 cc) e con RI più alto (0,76 vs. 0,68) (p<0,01) rispetto ai SKT.ConclusioniL’USD fornisce utili informazioni nei pazienti con DKT, permettendo il riscontro di anomalie asintomatiche unilaterali non clinicamente sospette; a livelli comparabili di funzione renale, i pazienti con DKT hanno valori di RI più alti e volume renale inferiore rispetto ai pazienti con SKT.

Ultrasound findings in dual kidney transplantation@@@Valutazione eco-color Doppler nel doppio trapianto di rene

PurposeThis study was done to analyse colour Doppler ultrasound (CDUS) findings in patients with dual kidney transplantation (DKT) and to compare renal volume and resistive index (RI) values between DKT and single kidney transplantation (SKT).Materials and methodsWe reviewed the clinical and imaging findings [30 CDUS, five magnetic resonance (MR) and one computed tomography (CT) examination] in 30 patients with DKT (23 men and seven women; median age 65 years; range 55–82). Three patients had clinical signs of graft malfunction. Renal volumes and RI were compared with those of 14 SKT patients and comparable levels of renal function.ResultsThree patients had graft dysfunction: one had chronic rejection and two had pathologies involving one kidney only (one encrusted pyeloureteritis of a left graft and one occluded main artery of a left graft). Asymptomatic unilateral pathologies were seen in six cases. In asymptomatic DKT patients, no significant differences in length, volume, cortical echogenicity and RI between the two kidneys were observed; DKTs were smaller (median volume 116.7 vs. 171.6 cc) and had higher RIs (0.76 vs. 0.68) (p<0.01) than SKTs.ConclusionsCDUS provides useful information in patients with DKT, allowing detection of clinically unsuspected unilateral diseases. At comparable levels of renal function, DKT patients had higher RI and lower volumes than SKT patients.RiassuntoObiettivoScopo del presente lavoro è stato analizzare gli aspetti eco-color Doppler (USD) in pazienti con trapianto di doppio rene (DKT) e paragonare volume renale e indice di resistenza (RI) nei pazienti con DKT e con trapianto di rene singolo da donatore ideale (SKT).Materiali e metodiAbbiamo valutato i dati clinici e di imaging [30 USD, 5 risonanze magnetiche (RM) e 1 tomografia computerizzata (TC)] in 30 pazienti con DKT (23 maschi e 7 femmine, età media 65 anni; range 55–82) paragonando volume renale e RI con quelli di 14 pazienti con SKT e livelli simili di funzione renale.RisultatiTre pazienti avevano disfunzione del trapianto: uno con rigetto cronico e due con patologie coinvolgenti un solo rene (1 pielonefrite incrostata rene sinistro e 1 occlusione dell’arteria renale sinistra). Alterazioni asintomatiche unilaterali sono state riscontrate in 6 ulteriori pazienti. Nei DKT asintomatici non sono state riscontrate differenze significative di lunghezza, volume, ecogenicità corticale e RI tra i due reni; nei DKT i reni erano più piccoli (volume 116,7 vs. 171,6 cc) e con RI più alto (0,76 vs. 0,68) (p<0,01) rispetto ai SKT.ConclusioniL’USD fornisce utili informazioni nei pazienti con DKT, permettendo il riscontro di anomalie asintomatiche unilaterali non clinicamente sospette; a livelli comparabili di funzione renale, i pazienti con DKT hanno valori di RI più alti e volume renale inferiore rispetto ai pazienti con SKT.