Early intensification and autologous stem cell transplantation in patients with systemic AL amyloidosis: a single-centre experience.

Primary systemic amyloidosis (AL amyloidosis) continues to have a very poor prognosis. Most therapeutic strategies remain unsatisfactory. Conventional chemotherapy is known to offer at best only moderate efficacy. Several studies have yielded higher complete response rates after high-dose chemotherapy and autologous stem cell transplantation (ASCT) in addition to improving outcomes in a subgroup of patients. However, the superiority of an intensive approach in AL amyloidosis has not been confirmed in a randomised trial. The precise role of ASCT remains unclear. We report our experience in 16 patients diagnosed with AL amyloidosis and treated in a multidisciplinary approach with high-dose melphalan and ASCT. Median age was 59 (39-71) years. The kidneys were predominantly affected in 75% of cases; two or more organs were affected in 38%. Median time from diagnosis to transplantation was 2 (1-4) months. Three patients (19%) developed acute renal failure and required transient dialysis. Transplant-related mortality was 6% after 100 days. Haematological complete response (CR) was obtained in nine (56%) and organ response in six (38%) patients. Nine out of 12 patients (75%) with kidney involvement exhibited a sustained clinical benefit at 12 months. Half of all the patients (n = 8) were alive after a median follow-up of 33 months, including two in continuous CR. This suggests that high-dose chemotherapy and ASCT are still valid treatment options in AL amyloidosis and that a significant number of patients with renal involvement might benefit from this approach.

Neuroarthropathy of the foot revealing primary systemic amyloidosis: case report and literature review.

The aims of this review were to describe the case of a patient with debilitating neuroarthropathy of the ankles and feet and reveal a primary systemic (amyloid light chain, AL) amyloidosis and to review the relevant literature concerning the peripheral neuropathy and neuroarthropathy due to amyloidosis. We will emphasize the diagnostic pitfalls and discuss prognosis and treatments of both the peripheral neuropathy and the arthropathy related to AL amyloidosis. This is a descriptive case report of a patient with neuroarthropathy of the lower limbs due to AL amyloidosis. A review and discussion of relevant literature were conducted, based on a PubMed search from 1973 to December 2013. A 51-year-old female was diagnosed with AL amyloidosis after 20 months of investigation of small painful deformities of the feet. Chronic peripheral neuropathy occurs as a manifestation of AL amyloidosis in 25 % of cases. It may exceptionally be complicated by neuroarthropathy. In this case, the paucity of clinical and electrophysiological signs of the neuropathy delayed the diagnosis, leading to a severe arthropathy. The massive destruction of the joints dominated the clinical and the poor functional outcome. Diagnosis of AL amyloidosis should be considered in the presence of a mild peripheral neuropathy and a distal destructive and painless arthropathy. The two key diagnostic procedures are serum protein electrophoresis and nerve biopsy. Delay in treatment worsens the prognosis.

AA amyloidosis treated with tocilizumab: case series and updated literature review.

BACKGROUND: In published case reports, tocilizumab (TCZ) has shown good efficacy for AA amyloidosis in almost all patients. We investigated the efficacy and safety of TCZ in AA amyloidosis in a multicentre study of unselected cases. METHODS: We e-mailed rheumatology and internal medicine departments in France, Switzerland and North Africa by using the Club Rhumatismes Inflammation (CRI) network and the French TCZ registry, Registry RoAcTEmra (REGATE), to gather data on consecutive patients with histologically proven AA amyloidosis who had received at least one TCZ infusion. Efficacy was defined as a sustained decrease in proteinuria level and/or stable or improved glomerular filtration rate (GFR) and by TCZ maintenance. RESULTS: We collected 12 cases of AA amyloidosis treated with TCZ as monotherapy (mean age of patients 63 ± 16.2 years, amyloidosis duration 20.6 ± 31.3 months): eight patients had rheumatoid arthritis (RA), six with previous failure of anti-tumor necrosis factor α (anti-TNF-α) therapy. In total, 11 patients had renal involvement, with two already on hemodialysis (not included in the renal efficacy assessment). For the nine other patients, baseline GFR and proteinuria level were 53.6 ± 32.8 mL/min and 5 ± 3.3 g/24 h, respectively. The mean follow-up was 13.1 ± 11 months. TCZ was effective for six of the eight RA patients (87.5%) according to European League Against Rheumatism response criteria (four good and two moderate responders). As expected, C-reactive protein (CRP) level decreased with treatment for 11 patients. Renal amyloidosis (n = 9) progressed in three patients and was stabilized in three. Overall, three patients showed improvement, with sustained decrease in proteinuria level (42%, 82% and 96%). Baseline CRP level was higher in subsequent responders to TCZ than other patients (p = 0.02). Among the six RA patients with previous anti-TNF-α therapy, amyloidosis was ameliorated in one and stabilized in three. Three serious adverse events occurred (two diverticulitis and one major calciphylaxia due to renal failure). Finally, 7 of 12 (58%) patients continued TCZ. CONCLUSIONS: The efficacy of TCZ for AA amyloidosis varies depending on the inflammatory status at treatment onset. Discrepancies between our study of unselected consecutive patients and reported cases may be due to publication bias. These results support further prospective trials of TCZ for AA amyloidosis.

Hidrocolpo por ectopia ureteral em hemivagina associado a displasia renal: relato de caso e revisão da literatura

Os autores apresentam um caso de displasia renal associada a ectopia ureteral vaginal homolateral, com uretero-hidronefrose contralateral devida a compressão por hidrocolpo causado pela ectopia e por um septo vaginal oblíquo. Os exames de imagem utilizados foram urografia excretora, cistografia, ultra-sonografia, tomografia computadorizada e cintilografia renal com Tc-99m-DMSA. Foi realizada revisão da literatura sobre casos de hidrocolpo associado a malformações urinárias.

Formato da onda do jato ureteral ao estudo Doppler espectral: comparação interobservadores. Estudo prospectivo em crianças assintomáticas

OBJETIVO: Diagnóstico precoce de distúrbios miccionais pode diminuir as repercussões sociais e psicológicas e evitar lesões renais. O jato ureteral pode ser avaliado por estudo Doppler, método que apresenta boa associação com dados clínicos dos pacientes no que diz respeito ao diagnóstico de disfunção miccional. O objetivo deste estudo é avaliar a concordância interobservadores entre os tipos de jato ureteral. MATERIAIS E MÉTODOS: Estudo prospectivo de concordância interobservadores. Um total de 41 pacientes foi examinado sequencialmente por dois médicos ultrassonografistas. Para cada paciente, três curvas dopplerfluxométricas foram obtidas de jatos consecutivos de cada ureter. O número de picos em cada curva foi observado e classificado. A velocidade máxima do maior pico de cada onda foi observada. Coeficientes kappa (κ) foram calculados. RESULTADOS: A concordância interobservadores foi moderada (κ = 0,48; intervalo de confiança 95%: 0,36-0,60). O padrão platô foi o mais frequente. As velocidades máximas dos ureteres, medidas pelos dois observadores, foram de 32,37 cm/s e 35,63 cm/s, respectivamente. CONCLUSÃO: O exame das curvas dopplerfluxométricas do jato ureteral é método que demonstrou moderada concordância interobservadores.

Ureteral reconstruction with abdominal wall muscle flap: experimental study in rabbits

The authors detail the experimental development of a technique for the reconstruction of the ureter using a tubular shape, muscle flap of the abdominal wall. the preliminary results indicate the feasibility of this surgical technique.

Estudo da ocorrência de litíase renal e ureteral em gatos com doença renal crônica

Investigou-se a ocorrência de nefrolitíase e/ou ureterolitíase em 72 gatos portadores de doença renal crônica (DRC), classificados predominantemente no estágio II, segundo os critérios designados pela IRIS - International Renal Interest Society. Destes pacientes, 47 (65,27%) apresentaram litíase renal e ou ureteral. Não houve diferença estatística entre o grupo de estudo (DRC com cálculo) e o grupo controle (DRC sem cálculo) em relação à idade (p=0,274). Apesar disso, os pacientes portadores de nefrolitíase e/ou ureterolitíase apresentaram maiores indícios de lesão renal, caracterizados por diferenças estatisticamente relevantes da densidade urinária (p=0,013) e pelo menor tamanho dos rins direito (p=0,009) e esquerdo (p=0,048). Encontrou-se similaridade entre os grupos em relação a outros parâmetros, tais como as concentrações plasmáticas de cálcio total, cálcio ionizado, fósforo, sódio, potássio e paratormônio intacto (PTHi). Os valores das concentrações séricas de ureia e bicarbonato diferiram entre os grupos, com valores de p=0,039 e p=0,037, respectivamente. Além disso, foi mensurada a pressão arterial, que se manteve inalterada na comparação entre o grupo de estudo e o grupo controle. Os resultados obtidos reforçam a necessidade de acompanhamento ultrassonográfico de todos os pacientes portadores de DRC, mesmo daqueles assintomáticos ou em estágios iniciais da doença.

An experimental model for the measurement of renal function after temporary ureteral obstruction in the rat

We present the results obtained with a ureterovesical implant after ipsilateral ureteral obstruction in the rat, suitable for the study of renal function after deobstruction in these animals. Thirty-seven male Wistar rats weighing 260 to 300 g were submitted to distal right ureteral ligation and divided into 3 groups, A (N = 13, 1 week of obstruction), B (N = 14, 2 weeks of obstruction) and C (N = 10, 3 weeks of obstruction). The animals were then submitted to ureterovesical implantation on the right side and nephrectomy on the left side. During the 4-week follow-up period serum levels of urea and creatinine were measured on the 2nd, 7th, 14th, 21st and 28th day and compared with preoperative levels. The ureterovesical implantation included a psoas hitch procedure and the ureter was pulled into the bladder using a transvesical suture. During the first week of the postoperative period 8 animals died, 4/13 in group A (1 week of obstruction) and 4/14 in group B (2 weeks of obstruction). When compared to preoperative serum levels, urea and creatinine showed a significant increase (P<0.05) on the 2nd postoperative day in groups A and B, with a gradual return to lower levels. However, the values in group B animals were higher than those in group A at the end of the follow-up. In group C, 2/10 animals (after 3 weeks of obstruction) were sacrificed at the time of ureterovesical implantation due to infection of the obstructed kidneys. The remaining animals in this group were operated upon but all of them died during the first week of follow-up due to renal failure. This technique of ureterovesical implantation in the rat provides effective drainage of the upper urinary tract, permitting the development of an experimental model for the study of long-term renal function after a period of ureteral obstruction

Dermatan sulfate reduces monocyte chemoattractant protein 1 and TGF-β production, as well as macrophage recruitment and myofibroblast accumulation in mice with unilateral ureteral obstruction

Selectins play an essential role in most inflammatory reactions, mediating the initial leukocyte-rolling event on activated endothelium. Heparin and dermatan sulfate (DS) bind and block P- and L-selectin function in vitro. Recently, we reported that subcutaneous administration of DS inhibits colon inflammation in rats by reducing macrophage and T-cell recruitment and macrophage activation. In the present study, we examined the effect of porcine intestinal mucosa DS on renal inflammation and fibrosis in mice after unilateral ureteral obstruction (UUO). Twenty-four adult male Swiss mice weighing 20-25 g were divided into 4 groups: group C (N = 6) was not subjected to any surgical manipulation; group SH (N = 6) was subjected to surgical manipulation but without ureter ligation; group UUO (N = 6) was subjected to unilateral ureteral obstruction and received no treatment; group UUO plus DS (N = 6) was subjected to UUO and received DS (4 mg/kg) subcutaneously daily for 14 days. An immunoblot study was also performed for TGF-β. Collagen (stained area ~3700 µm²), MCP-1 (stained area ~1700 µm²), TGF-β (stained area ~13% of total area), macrophage (number of cells ~40), and myofibroblast (stained area ~1900 µm²) levels were significantly (P < 0.05) higher in the UUO group compared to control. DS treatment significantly (P < 0.05) reduced the content of collagen (stained area ~700 µm²), MCP-1 (stained area ~160 µm²) and TGF-β (stained area ~5% of total area), in addition to myofibroblast (stained area ~190 µm²) and macrophage (number of cells ~32) accumulation in the obstructed kidney. Overall, these results indicate that DS attenuates kidney inflammation by reducing macrophage recruitment, myofibroblast population and fibrosis in mice submitted to UUO.

N-acetylcysteine protects against renal injury following bilateral ureteral obstruction

Background. Obstructive nephropathy decreases renal blood flow (RBF) and glomerular filtration rate (GFR), causing tubular abnormalities, such as urinary concentrating defect, as well as increasing oxidative stress. This study aimed to evaluate the effects of N-acetylcysteine (NAC) on renal function, as well as on the protein expression of aquaporin 2 (AQP2) and endothelial nitric oxide synthase (eNOS), after the relief of bilateral ureteral obstruction (BUO). Methods. Adult male Wistar rats were divided into four groups: sham (sham operated); sham operated + 440 mg/kg body weight (BW) of NAC daily in drinking water, started 2 days before and maintained until 48 h after the surgery; BUO (24-h BUO only); BUO + NAC-pre (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started 2 days before BUO); and BUO + NAC-post (24-h BUO plus 440 mg/kg BW of NAC daily in drinking water started on the day of BUO relief). Experiments were conducted 48 h after BUO relief. Results. Serum levels of thiobarbituric reactive substances, which are markers of lipid peroxidation, were significantly lower in NAC-treated rats than in the BUO group rats. The administration of NAC provided significant protection against post-BUO GFR drops and reductions in RBF. Renal cortices and BUO rats presented decreased eNOS protein expression of eNOS in the renal cortex of BUO group rats, whereas it was partially recovered in BUO + NAC-pre group rats. Urine osmolality was significantly lower in BUO rats than in sham group rats or NAC-treated rats, the last also presenting less interstitial fibrosis. Post-BUO downregulation of AQP2 protein expression was averted in the BUO + NAC-pre group rats. Conclusions. This study demonstrates that NAC administration ameliorates the renal function impairment observed 48 h after the relief of 24-h BUO. Oxidative stress is important for the suppression of GFR, RBF, tissue AQP2 and eNOS in the polyuric phase after the release of BUO.

Ureteroscopy in Pregnant Women for Ureteral Stone

Introduction: The occurrence of urolithiasis in pregnancy represents a challenge in both diagnosis and treatment of this condition, because it presents risks not only to the mother but also to the fetus. Surgical treatment may be indicated for patients with infection, persistent pain, and obstruction of a solitary kidney. We present our experience on the management of pregnant patients with ureteral calculi and a review of the literature.Materials and Methods: The charts of 19 pregnant patients with obstructive ureteral calculi were retrospectively reviewed. Gestational age ranged from 13 to 33 weeks. In all patients, ureteral stone was diagnosed on abdominal ultrasound. In regard to localization, 15 calculi were in the distal ureter, 3 in the proximal ureter, and 1 in the interior of an ureterocele. Calculi size ranged from 6 to 10 mm (mean, 8 mm). The following criteria were used to indicate ureteroscopy: persistent pain with no improvement after clinical treatment, increase in renal dilation, or presence of uterine contractions. Nine patients (47.3%) were submitted to ureteroscopy. All calculi (100%) were removed with a stone basket extractor under continuous endoscopic vision. None of the calculi demanded the use of a lithotriptor.Results: Nine patients (47.3%) treated with clinical measurements presented no obstetric complications and spontaneous elimination of the calculi. Nine patients (47.3%) submitted to ureteroscopy had no surgical complications. There was remission of pain in all cases after ureteroscopy and ureteral catheter placement.Conclusion: The diagnosis and treatment of ureteral lithiasis in pregnant women present potential risks for the fetus and the mother. Conservative management is the first option, but ureteroscopy may be performed with safety and high success rates.

Primary cutaneous amyloidosis: Clinical, laboratorial and histopathological study of 25 cases. Identification of gammaglobulins and C3 in the lesions by immunofluorescence

25 cases of primary cutaneous amyloidosis are studied. 16 patients had macular amyloidosis (MPA) and 9 lichen amyloidosus (LPA). γ-Globulins were increased in 50% of the patients. IgG and IgA were increased in the serum of 5 and 3 patients with MPA and 4 and 2 patients with LPA, respectively. Volume of amyloid deposits was similar in both forms. By direct immunofluorescence we demonstrated IgG in the amyloid deposits of 21 of the 25 cases and C3 in 13; IgM was present in 9 cases of MPA and in 3 cases of LPA. MPA was more frequent than LPA; histologically, it was impossible to distinguish MPA from LPA; correlation between serum levels of γ-globulins and their presence in amyloid deposits was weak; MPA and LPA seem to be distinct clinical manifestations of the same disease and itching does not cause transformation of MPA in LPA.

Silent Ureteral Stones: Impact on Kidney Function-Can Treatment of Silent Ureteral Stones Preserve Kidney Function?

OBJECTIVE To report our experience with silent ureteral stones and expose their true influence on renal function. METHODS We analyzed 506 patients who had undergone ureterolithotripsy from January 2005 to May 2010. Silent ureteral stones were calculi found in the absence of any specific or subjective ureteral stone-related symptoms. Of the 506 patients, 27 (5.3%) met these criteria (global cohort). All patients were assessed postoperatively with dimercaptosuccinic acid scintigraphy (DMSA). A difference in relative kidney function of >10% was considered abnormal. Pre- and postoperative comparative DMSA analyses were electively obtained for 9 patients (kidney function cohort). A t test was used to assess the numeric variables, and the chi-square test or Fisher's exact test was used for categorical variables. Two-tailed P < .05 was considered statistically significant. RESULTS Stones were diagnosed by radiologic abdominal evaluation for nonurologic diseases in 40% and after previous nephrolithiasis treatment in 33%. The primary therapy was ureterolithotripsy in 88%. The mean follow-up time was 23 months. The overall ureteral stone-free rate after 1 and 2 procedures was 96% and 100%, respectively. In the global cohort, the mean pre- and postoperative serum creatinine levels were similar (P = .39), and the mean postoperative function on DMSA was 31%. In the kidney function cohort, no difference was found between the pre-and postoperative DMSA findings (22% +/- 12.1% vs 20% +/- 11.8%; P = .83) and serum creatinine (0.8 +/- 0.13 mg/dL vs 1.0 +/- 0.21 mg/dL; P = .45). CONCLUSION Silent ureteral stones are associated with decreased kidney function present at the diagnosis. Hydronephrosis tends to diminish after stone removal, and kidney function remains unaltered. UROLOGY 79: 304-309, 2012. (C) 2012 Elsevier Inc.