Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.

BACKGROUND: Autosomal dominant polycystic kidney disease slowly progresses to end-stage renal disease and has no effective therapy. A pilot study suggested that the somatostatin analogue octreotide longacting release (LAR) could be nephroprotective in this context. We aimed to assess the effect of 3 years of octreotide-LAR treatment on kidney and cyst growth and renal function decline in participants with this disorder. METHODS: We did an academic, multicentre, randomised, single-blind, placebo-controlled, parallel-group trial in five hospitals in Italy. Adult (>18 years) patients with estimated glomerular filtration rate (GFR) of 40 mL/min per 1·73 m(2) or higher were randomly assigned (central allocation by phone with a computerised list, 1:1 ratio, stratified by centre, block size four and eight) to 3 year treatment with two 20 mg intramuscular injections of octreotide-LAR (n=40) or 0·9% sodium chloride solution (n=39) every 28 days. Study physicians and nurses were aware of the allocated group; participants and outcome assessors were masked to allocation. The primary endpoint was change in total kidney volume (TKV), measured by MRI, at 1 year and 3 year follow-up. Analyses were by modified intention to treat. This study is registered with ClinicalTrials.gov, NCT00309283. FINDINGS: Recruitment was between April 27, 2006, and May 12, 2008. 38 patients in the octreotide-LAR group and 37 patients in the placebo group had evaluable MRI scans at 1 year follow-up, at this timepoint, mean TKV increased significantly less in the octreotide-LAR group (46·2 mL, SE 18·2) compared with the placebo group (143·7 mL, 26·0; p=0·032). 35 patients in each group had evaluable MRI scans at 3 year follow-up, at this timepoint, mean TKV increase in the octreotide-LAR group (220·1 mL, 49·1) was numerically smaller than in the placebo group (454·3 mL, 80·8), but the difference was not significant (p=0·25). 37 (92·5%) participants in the octreotide-LAR group and 32 (82·1%) in the placebo group had at least one adverse event (p=0·16). Participants with serious adverse events were similarly distributed in the two treatment groups. However, four cases of cholelithiasis or acute cholecystitis occurred in the octreotide-LAR group and were probably treatment-related. INTERPRETATION: These findings provide the background for large randomised controlled trials to test the protective effect of somatostatin analogues against renal function loss and progression to end-stage kidney disease. FUNDING: Polycystic Kidney Disease Foundation.

Gross hematuria due to acquired haemophilia in hereditary hemorrhagic telangiectasia.

Hereditary haemorrhagic telangiectasia (HHT, Osler-Weber-Rendu syndrome) is a rare inherited disease; acquired haemophilia, caused by factor VIII inhibitors, is a rare autoimmune disorder. Both diseases cause bleeding manifestations. We report a case of a young woman affected by hereditary haemorrhagic telangiectasia who was admitted to our unit because of gross hematuria. The prolonged activated partial thromboplastin time suggested us the possibility of a bleeding cause other than hereditary haemorrhagic telangiectasia. The test result for factor VIII inhibitors resulted positive and a diagnosis of acquired haemophilia was made. The patient was treated with frozen fresh plasma and with activated eptacog alpha and a steroid therapy was started. After she received steroid, factor VIII inhibitor titre decreased and activated partial thromboplastin time gradually recovered. After 2 weeks a complete normalization of activated partial thromboplastin time was obtained. Acquired haemophilia is a life-threatening disorder. Measuring factor VIII activity and its inhibitor in patients with bleeding and a prolonged activated partial thromboplastin time are recommended even in patients affected by other known hemorrhagic disease.

[Census of the renal and dialysis units by Italian Society of Nephrology: nephrologist's workload for renal patient assistance in Italy (2014-2015)]. / Censimento a cura della Società Italiana di Nefrologia delle strutture nefrologiche e della loro attività in Italia nel 2014-2015: il lavoro del nefrologo.

BACKGROUND: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted acensusof the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to theyear 2014. METHODS: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit. RESULTS: Renal and dialysis activity was performed by over 2718 physicians (45 pmp). The management of the acute renal failure was one of the most frequent activities in the public renal units (12,206 patients in ICU and 140.00 dialysis sessions). There were performed about 9000 AV fistulas and 1700 central vascular catheters insertions. In the census, there are a lot of data regarding organization, workforce and workload of the renal unit in Italy. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

[Census of the renal and dialysis units by Italian Society of Nephrology: structure and organization for renal patient assistance in Italy (2014-2015)]. / Censimento a cura della Società Italiana di Nefrologia delle strutture nefrologiche e delle loro attività in Italia nel 2014-2015: l'organizzazione.

BACKGROUND: Given the public health challenge and burden of chronic kidney disease, the Italian Society of Nephrology (SIN) promoted a census of the renal and dialysis units to analyse structural and human resources, organizational aspects, activities and workload referring to the year 2014. METHODS: An online questionnaire, including 64 items exploring structural and human resources, organization aspects, activities and epidemiological data referred to 2014, was sent to chiefs of any renal or dialysis unit. RESULTS: 615 renal units were identified. From these 615 units, 332 were public renal centres (of which 318 centres answered to the census) and 283 were private dialysis centres (of which 113 centres answered to the census). The results show 6 public renal units pmp. Renal biopsies were 4624 (81 pmp). The nephrology beds are about 41 pmp. There are 7.304 nurses working in HD wards, 1.692 in the nephrology wards and only 613 for outpatients clinics. The benchmark data derived from this census show interesting comparisons between centres, regions and groups of regions. These data realised the clinical management of renal disease in Italy.

[Quality of life and hemodialysis]. / La qualità della vita in una popolazione di pazienti in trattamento emodialitico.

The periodic study of Quality of Life ( QoL) in chronic uremic patients on hemodialysis, is a tool aimed to adapt the approach to the patient, according to the evolving needs. The study sample consisted of 35 subjects (M 65.7% and 34.2 % F), aged 18-84 years (57+16,3) and with an average dialytic age of 6.5 years (+5.3). The tool used was the Multidimensional Inventory for Patient on Hemodialysis (IPPE) which provides a survey for the patients consisting of 24 items to evaluate their degree of agreement/disagreement on a 4-point Lickert scale (false, partially false, partially true, true). The analysis showed that: with respect to the family relationships, criticality was 12.6 %, about the relationship with their body it was 15,8 %, regarding the need to drink it was 22.2%, about the daily life 20.6% and about the perception of their disease it was 7.9 %. Compared to the Index of Global Psychophysical Distress (IPPE), in the sample considered the 67,6% of the patients did not present any problem, the 32.3 % presented a quite critical discomfort and nobody presented any acute critical discomfort. Statistical analysis showed a significant inverse correlation between the IPPE and dialysis age (r = - 0.473, p = 0.005). Although this is a preliminary result of an in-depth understanding of the underlying processes, it may help to identify the factors that, over time, contribute to the patient adaptation to the dialysis treatment, in order to facilitate this process in people who start hemodialysis.

Acute interstitial nephritis, a rare complication of Giardiasis.

Acute interstitial nephritis is a relevant cause of acute renal failure. Drugs are the predominant cause, followed by infections and idiopathic lesions. Acute interstitial nephritis as a form of hypersensitivity reaction is an uncommon manifestation in the setting of human parasitic infections. We present a case of acute interstitial nephritis in association with Giardia infection in a 54-year-old woman who developed an impairment of renal function after a prolonged period of slight fever and diarrhea. After an attempt to recover renal impairment by vigorous rehydratation, because of the unclear origin of the persisting renal failure, a percutaneous renal biopsy was performed and a diagnosis of severe acute interstitial nephritis was made. Steroid therapy was started and after six weeks, renal function had completely recovered. In cases of unexplained renal failure in patients affected by parasitic infections, interstitial nephritis should be considered and it is our opinion that a renal biopsy should be always performed.

Measuring and estimating GFR and treatment effect in ADPKD patients: results and implications of a longitudinal cohort study.

Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m(2) in 111 and 71 ADPKD patients, respectively. CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research.

Juxta-anastomotic stenosis of native arteriovenous fistulas: surgical treatment versus percutaneous transluminal angioplasty.

PURPOSE: Juxta-anastomotic stenosis (JAS) is a complication of arteriovenous fistulas (AVFs). Both surgical revision (SR) and percutaneous transluminal angioplasty (PTA) may correct JAS. In this study we compare the results for SR treatment versus PTA. METHODS: From January 2005 until December 2008, 66 PTA and 68 SR were performed in 43 and 57 uremic pts with JAS of the native AVF, respectively. Efficacy of SR and PTA was evaluated measuring brachial arterial flow (BAF) by CDU. The Kaplan-Meier table of primary and assisted primary patency was analyzed. RESULTS: PTA was attempted in 50 patients. PTA failed in 7 patients and they were switched to SR. In 43 pts, PTA produced a favorable effect, with a mean increase of 99 ± 70% (p<0.001) in blood flow. Restenosis occurred in 17 pts: 2 were treated by SR and 15 by PTA. Restenosis occurred again in 6/15 pts: after second restenosis, 5/6 pts received a third PTA with stenting, 1 patient underwent SR. The failure of access occurred after 12-17 months in 3 pts. In 57/57 JAS treated by SR, a new well-functioning fistula was created upstream of the stenosis, with a mean increase of 102 ± 71% in blood flow (p<0.001). Restenosis occurred in 15 pts: 9 were treated by SR and 6 by PTA. Access failure occurred after 3-36 months in 9 pts. The Kaplan-Meier table showed a better primary patency for SR (p<0.05) without difference in assisted primary patency. CONCLUSIONS: SR showed a better primary patency then PTA, confirming the trend to stenosis relapse after PTA. So, as PTA does not exclude a later correction of the JAS, the similar assisted patency suggests to perform a PTA first, reserving SR for after its failure.