Renal involvement in sarcoidosis: histological patterns and prognosis, an Italian survey.

BACKGROUND: Granulomatous interstitial nephritis in sarcoidosis (sGIN) is generally clinically silent, but in <1% causes acute kidney injury (AKI). METHODS: This Italian multicentric retrospective study included 39 sarcoidosis-patients with renal involvement at renal biopsy: 31 sGIN-AKI, 5 with other patterns (No-sGIN-AKI), 3 with nephrotic proteinuria. We investigate the predictive value of clinical features, laboratory, radiological parameters and histological patterns regarding steroid response. Primary endpoint: incident chronic kidney disease (CKD) beyond the 1°follow-up (FU) year; secondary endpoint: response at 1°line steroid therapy; combined endpoint: the association of initial steroid response and outcome at the end of FU. RESULTS: Complete recovery in all 5 No-sGIN-AKI-patients, only in 45% (13/29) sGIN-AKI-patients (p=0.046) (one lost in follow-up, for another not available renal function after steroids). Nobody had not response. Primary endpoint of 22 sGIN-AKI subjects: 65% (13/20) starting with normal renal function developed CKD (2/22 had basal CKD; median FU 77 months, 15-300). Combined endpoint: 29% (6/21) had complete recovery and final normal renal function (one with renal relapse), 48% (10/21) had partial recovery and final CKD (3 with renal relapse, of whom one with basal CKD) (p=0.024). Acute onset and hypercalcaemia were associated to milder AKI and better recovery than subacute onset and patients without hypercalcaemia, women had better endpoints than men. Giant cells, severe interstitial infiltrate and interstitial fibrosis seemed negative predictors in terms of endpoints. CONCLUSIONS: sGIN-AKI-patients with no complete recovery at 1°line steroid should be treated with other immunosuppressive to avoid CKD, in particular if males with subacute onset and III stage-not hypercalcaemic AKI.

[Environmental toxicity and direct renal toxicity from drugs: herbs and plants].

Traditional medicine is a widespread treatment method in the world. Despite the WHO's confirmation of the progressive spread of national policies responsible for controlling the production and distribution of phytotherapy, the risk of toxic side effects is high even if the real incidence is not known. These risks largely result from the self-prescription supported by the assumption that what is natural is not dangerous to health. The phytotherapic industry turnover is progressively increasing, favored by the ease with which products can be purchased without prescription in pharmacies in some countries or online. In particular, Chinese herbs can be nephrotoxic and clinicians should consider the possibility of their role in some cases of AKI or CKD with unknown etiology. Furthermore, in the collection of the pharmacological history of patients with CKD or kidney transplantation it is necessary to exclude the use of some phytotherapics of common use that may be contraindicated for possible interactions with drugs of conventional medicine.

[Vascular access survey in the Triveneto area: data analysis for the year 2017].

In 2017 the Italian Society of Nephrology operating in the Triveneto area investigated through a questionnaire, distributed to the various nephrological centers in the regions of Friuli Venezia Giulia, Trentino Alto Adige and Veneto, the differences concerning organizational models, choice of dialysis, creation and management of vascular access. The results emerging from the analysis of the collected data are presented.

Octreotide-LAR in later-stage autosomal dominant polycystic kidney disease (ALADIN 2): A randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent genetically determined renal disease. In affected patients, renal function may progressively decline up to end-stage renal disease (ESRD), and approximately 10% of those with ESRD are affected by ADPKD. The somatostatin analog octreotide long-acting release (octreotide-LAR) slows renal function deterioration in patients in early stages of the disease. We evaluated the renoprotective effect of octreotide-LAR in ADPKD patients at high risk of ESRD because of later-stage ADPKD. METHODS AND FINDINGS: We did an internally funded, parallel-group, double-blind, placebo-controlled phase III trial to assess octreotide-LAR in adults with ADPKD with glomerular filtration rate (GFR) 15-40 ml/min/1.73 m2. Participants were randomized to receive 2 intramuscular injections of 20 mg octreotide-LAR (n = 51) or 0.9% sodium chloride solution (placebo; n = 49) every 28 days for 3 years. Central randomization was 1:1 using a computerized list stratified by center and presence or absence of diabetes or proteinuria. Co-primary short- and long-term outcomes were 1-year total kidney volume (TKV) (computed tomography scan) growth and 3-year GFR (iohexol plasma clearance) decline. Analyses were by modified intention-to-treat. Patients were recruited from 4 Italian nephrology units between October 11, 2011, and March 20, 2014, and followed up to April 14, 2017. Baseline characteristics were similar between groups. Compared to placebo, octreotide-LAR reduced median (95% CI) TKV growth from baseline by 96.8 (10.8 to 182.7) ml at 1 year (p = 0.027) and 422.6 (150.3 to 695.0) ml at 3 years (p = 0.002). Reduction in the median (95% CI) rate of GFR decline (0.56 [-0.63 to 1.75] ml/min/1.73 m2 per year) was not significant (p = 0.295). TKV analyses were adjusted for age, sex, and baseline TKV. Over a median (IQR) 36 (24 to 37) months of follow-up, 9 patients on octreotide-LAR and 21 patients on placebo progressed to a doubling of serum creatinine or ESRD (composite endpoint) (hazard ratio [HR] [95% CI] adjusted for age, sex, baseline serum creatinine, and baseline TKV: 0.307 [0.127 to 0.742], p = 0.009). One composite endpoint was prevented for every 4 treated patients. Among 63 patients with chronic kidney disease (CKD) stage 4, 3 on octreotide-LAR and 8 on placebo progressed to ESRD (adjusted HR [95% CI]: 0.121 [0.017 to 0.866], p = 0.036). Three patients on placebo had a serious renal cyst rupture/infection and 1 patient had a serious urinary tract infection/obstruction, versus 1 patient on octreotide-LAR with a serious renal cyst infection. The main study limitation was the small sample size. CONCLUSIONS: In this study we observed that in later-stage ADPKD, octreotide-LAR slowed kidney growth and delayed progression to ESRD, in particular in CKD stage 4. TRIAL REGISTRATION: ClinicalTrials.gov NCT01377246; EudraCT: 2011-000138-12.

Ultrasound findings of BK polyomavirus-associated nephropathy in renal transplant patients.

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised patients. BKV infection occurs in 1-9 % of renal transplants and causes chronic nephropathy or graft loss. Diagnosis of BKV-associated nephropathy (BKVAN) is based on detection of viruria then viremia and at least a tubule-interstitial nephritis at renal biopsy. This paper describes the ultrasound and color Doppler (US-CD) features of BKVAN. Seventeen patients affected by BKVAN were studied using a linear bandwidth 7-12 MHz probe. Ultrasound showed a widespread streak-like pattern with alternating normal echoic and hypoechoic streaks with irregular edges from the papilla to the cortex. Renal biopsy performed in hypoechoic areas highlighted the typical viral inclusions in tubular epithelial cells. Our experience suggests a possible role for US-CD in the non-invasive diagnosis of BKVAN when combined with blood and urine screening tests. US-CD must be performed with a high-frequency linear probe to highlight the streak-like pattern of the renal parenchyma.

[Karyomegalic interstitial nephritis: an atypical case]. / La nefrite interstiziale cariomegalica: descrizione di un caso clinico atipico.

Karyomegalic interstitial nephritis (KIN) is a rare disease entity that was first described by Burry in 1974. The prevalence of this disease is less than 1% and its pathogenesis is unclear. KIN is characterized by chronic tubulointerstitial nephritis associated with enlarged tubular epithelial cell nuclei, which leads to progressive decline of renal function. The disease has no known treatment. Here, we report on a 50-year-old female patient who presented with asymptomatic progressive decline of renal function. Renal biopsy demonstrated chronic tubulointerstitial nephritis with markedly enlarged and hyperchromic nuclei of tubule epithelial cells the hallmark of karyomegalic nephritis. Clinical and pathologic findings of this case are discussed in light of the available literature.

[Renal biopsy in the lateral position in high risk patients: an opportunity to take advantage of]. / La biopsia renale in decubito laterale nei pazienti complessi: una possibilità da sfruttare.

Percutaneous ultrasound-guided renal biopsy (RB) is the gold standard for diagnosis of renal diseases. The standard procedure involves biopsy in the prone position (PP) for the native kidneys. In high risk patients, transjugular and laparoscopic RB have been proposed. In patients suffering from obesity or respiratory diseases, the RB of the native kidney in the supine anterolateral position (SALP) represents an alternative to these invasive and expensive methods. We illustrate the technique of execution of RB in the lateral position (LP) on native kidneys. The procedure is safe, effective and has reduced the path travelled by the needle biopsy compared with PP and SALP.

Novel INF2 mutations in an Italian cohort of patients with focal segmental glomerulosclerosis, renal failure and Charcot-Marie-Tooth neuropathy.

BACKGROUND: Mutations of INF2 represent the major cause of familial autosomal dominant (AD) focal segmental glomerulosclerosis (FSGS). A few patients present neurological symptoms of Charcot-Marie-Tooth (CMT) disease but the prevalence of the association has not been assessed yet. METHODS: We screened 28 families with AD FSGS and identified 8 INF2 mutations in 9 families (32 patients overall), 3 of which were new. Mutations were in all cases localized in the diaphanous-inhibitory domain (DID) of the protein. RESULTS: Clinical features associated with INF2 mutations in our patient cohort included mild proteinuria (1.55 g/L; range 1-2.5) and haematuria as a unique symptom that was recognized at a median age of 21.75 years (range 8-30). Eighteen patients developed end-stage renal disease during their third decade of life; 12 patients presented a creatinine range between 1.2 and 1.5 mg/dL and 2 were healthy at 45 and 54 years of age. CMT was diagnosed in four cases (12.5%); one of these patients presented an already known mutation on exon 2 of INF2, whereas the other patients presented the same mutation on exon 4, a region that was not previously associated with CMT. CONCLUSIONS: We confirmed the high incidence of INF2 mutations in families with AD FSGS. The clinical phenotype was mild at the onset of the disease, but evolution to ESRD was frequent. The incidence of CMT has, for the first time, been calculated here to be 12.5% of mutation carriers. Our findings support INF2 gene analysis in families in which renal failure and/or neuro-sensorial defects are inherited following an AD model.

[Ultrasound-guided renal biopsy: evaluation of different models of biological simulator]. / La biopsia renale-ecoguidata: valutazione di diversi modelli di simulatore biologico.

Percutaneous ultrasound-guided renal biopsy is the gold standard for diagnosis and treatment of renal diseases. Recently, many studies strongly support the role of renal biopsy for the management of small renal mass. The experience of the operator is crucial in reducing the incidence of major complications. The use of simulators can accelerate the learning curve in those individuals who train in renal biopsy. We describe four simple and affordable phantoms for renal biopsy. The first two simulators were constructed by a porcine kidney wrapped in perirenal fat or covered by a flap of abdominal skin. The third simulator was constructed by embedding a porcine kidney in a turkey breast and olives to simulate the presence of small tumors. For the fourth model, we used the loin of a pork. Given the encouraging results of our in vitro study, we believe that simulators allow trainees to familiarize themselves with the handling of the equipment in an environment that is risk-free when compared to the clinical scenario.

[Goodpasture's disease: a case series]. / La Malattia di Goodpasture: l'esperienza di un singolo centro.

Goodpasture's disease (GD) is an uncommon and severe autoimmune disorder caused by circulating autoantibodies directed against the glomerular basement membrane cross-reacting with the alveolar basement membrane. GD is clinically characterized by rapidly progressive glomerulonephritis, often associated with pulmonary hemorrhage representing a nephrological emergency. We present the clinical features of 9 cases, diagnosed in 1997-2012, in our Renal Unit. Contrary to previous reports, we found a predominance of GD in females and we observed unusual clinical patterns, such as the association with renal vein thrombosis in a pregnant patient, thrombosis of the pulmonary arteries and a late isolated recurrence of alveolitis. In dialysis-dependent patients, renal transplantation can represent an available treatment option.

Lung ultrasound during hemodialysis: the role in the assessment of volume status.

OBJECTIVE: Fluid balance is important in patients undergoing hemodialysis. "Dry" weight is usually estimated clinically, and also, bioimpedance is considered reliable. Ultrasonography of inferior vena cava (IVC) estimates central venous pressure, and lung ultrasound evaluates extravascular (counting B-lines artifact) lung water. Our study was aimed to clarify their usefulness in the assessment of volume status during hemodialysis. METHODS: A total of 71 consecutive patients undergoing hemodialysis underwent lung and IVC ultrasound and bioimpedance spectroscopy immediately before and after dialysis. RESULTS: There was a significant reduction in the number of B-lines (3.13 vs 1.41) and in IVC diameters (end-expiratory diameter 1.71 vs 1.37; end-inspiratory diameter 1.19 vs 0.95) during dialysis. The reduction in B-lines correlated with weight reduction during dialysis (p 0.007); none of the parameters concerning the IVC correlated with fluid removal. At the end of the dialysis session, the total number of B-lines correlated with bioimpedance residual weight (p 0.002). DISCUSSION: The reduction in B-lines correlated with fluid loss due to hemodialysis, despite the small pre-dialysis number, confirming that lung ultrasound can identify even modest variations in extravascular lung water. IVC ultrasound, which reflects the intravascular filling grade, might not be sensitive enough to detect rapid volume decrease. Clinically estimated dry weight had a poor correlation with both bioimpedance and ultrasound techniques. Post-dialysis B-lines number correlates with residual weight assessed with bioimpedance, suggesting a role for ultrasound in managing hemodialysis patients.

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.

[A case of intrarenal hematoma: role of ultrasonography in the early diagnosis of a possible complication of anticoagulant therapy]. / Un caso di ematoma intrarenale: ruolo degli ultrasuoni nella diagnosi in urgenza di una possibile complicanza del trattamento anticoagulante.

Uremia associated with anticoagulant therapy is a high risk factor for bleeding complications in patients undergoing hemodialysis. We report a case of intrarenal hematoma arising in a uremic patient treated with warfarin. The hematoma was rapidly diagnosed by ultrasonography of the abdomen and treated with embolization. Our experience confirms that the availability of an ultrasound facility within the renal unit allows better assessment of our patients, also in the management of the most fearsome and rare complications. Moreover, it strengthens the evidence that uremic patients are at high risk of bleeding complications when treated with oral anticoagulants.

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.

[Herbal remedies: nephrotoxicity and drug interactions]. / Erbe: nefrotossicita' e interazioni farmacologiche.

The first reports of interstitial fibrosis leading to rapidly progressing chronic renal failure (CRF) in young women undergoing slimming treatment appeared at the beginning of the 1990s in Belgium. These slimming pills erroneously contained powdered roots of plants - picked in China - belonging to the Aristolochia instead of Stephania tetranda family. In the following years, after new cases had occurred worldwide, the term aristolochic acid nephropathy (AAN) came into use. Despite numerous warnings from various post-marketing surveillance institutes, products containing aristolochic acid are still widely used by Asiatic herbal practitioners and easily available on the Internet, where they are marketed without being subject to any regulations. In 2002 the IARC (International Agency for Research on Cancer) conclusively recognized the urothelial carcinogenicity of aristolochic acid. Because of the globalization and the growing use of phytotherapy worldwide, nephrologists should take into account AAN as a possible cause of CRF. In addition to assessing the direct kidney toxicity caused by some products used in phytotherapy, the authors conclude that it is necessary to research more closely possible drug interactions and side effects of commonly used herbs such as Echinacea, Gingko biloba, St. John's wort, ginseng, and garlic, which patients consider to be natural, non-toxic and self-prescribed remedies and whose use they therefore seldom disclose to their doctors.