Temsirolimus in overtreated metastatic renal cancer with subsequent use of sunitinib: A case report.

During the last decade, we have been developing new therapeutic strategies for the treatment of renal cancer, based on knowledge derived from molecular biology. We report a case of long-term renal metastatic cancer progression despite therapy with sunitinib and interleukin, which are the most active drugs in renal cancer. Disease stabilization for 58 weeks was achieved upon sequential use of temsirolimus, following the occurrence of disease progression during angiogenic therapy. The patient demonstrated excellent tolerance without marked symptoms for 10 months. Hypothyroidism and mumps-related adverse events were present. The survival time from diagnosis to lung metastasis was 8 years. Thus, this case demonstrates promising therapeutic effects of the sequential use of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors during different stages of the disease.

Estudio transversal sobre la prevalencia de la Enfermedad Metabólica Ósea (EMO) y Nutrición Parenteral Domiciliaria (NPD) en España: datos del Grupo NADYA

Patients with intestinal failure who receive HPN are at high risk of developing MBD. The origin of this bone alteration is multifactorial and depends greatly on the underlying disease for which the nutritional support is required. Data on the prevalence of this disease in our environment is lacking, so NADYA-SEMPE group has sponsored this transversal study with the aim of knowing the actual MBD prevalence. MATERIAL AND METHODS: Retrospective data from 51 patients from 13 hospitals were collected. The questionnaire included demographic data as well as the most clinically relevant for MBD data. Laboratory data (calciuria, PTH, 25 -OH -vitamin D) and the results from the first and last bone densitometry were also registered. RESULTS: Bone mineral density had only been assessed by densitometry in 21 patients at the moment HPN was started. Bone quality is already altered before HPN in a significant percentage of cases (52%). After a mean follow up of 6 years, this percentage increases up to 81%. Due to retrospective nature of the study and the low number of subjects included it has not been possible to determine the role that HPN plays in MBD etiology. Only 35% of patients have vitamin D levels above the recommended limits and the majority of them is not on specific supplementation. CONCLUSIONS: HPN is associated with very high risk of MBD, therefore, management protocols that can lead to early detection of the problem as well as guiding for follow up and treatment of these patients are needed.

Primary renal lymphoma: report of three new cases and literature review.

OBJECTIVES We report the cases of three patients with primary renal lymphoma. Diagnosis and subsequent treatment are discussed. METHODS The literature on the origin, epidemiology, clinical presentation, diagnosis, treatment and prognosis of primary renal lymphoma was reviewed. RESULTS The first patient was diagnosed after radical nephrectomy and subsequently was given six cycles of CVP (cyclophosphamide, vincristine, prednisone). The diagnosis of the second patient was established by renal biopsy, and the patient received six cycles of CHOP (cyclophosphamide, adriamycin, vincristine and predisone). The last patient had a lymphoma, secondary to immunosuppression, in a transplanted kidney. In this case transplant nephrectomy sufficed to cure the patient's lymphoma. All patients had B-cell non-Hodgkin lymphoma (an extrarenal origin was ruled out by bone marrow biopsy), and were disease-free 15 months, 7 months, and 6.5 years after diagnosis, respectively. CONCLUSIONS Primary renal lymphoma is rare. Diagnosis is established by renal biopsy, although it often presents as a mass simulating renal cell cancer and diagnosis is obtained after radical nephrectomy. Treatment consists of chemotherapy (CHOP). associated with rituximab.

Association of HbA1c and cardiovascular and renal disease in an adult Mediterranean population

BACKGROUND: Increasing evidence suggests a mechanistic link between the glycemic environment and renal and cardiovascular events, even below the threshold for diabetes. We aimed to assess the association between HbA1c and chronic kidney disease (CKD) and cardiovascular disease (CVD). METHODS: A cross-sectional study involving a random representative sample of 2270 adults from southern Spain (Malaga) was undertaken. We measured HbA1c, serum creatinine and albuminuria in fasting blood and urine samples. RESULTS: Individuals without diabetes in the upper HbA1c tertile had an unfavorable cardiovascular and renal profile and shared certain clinical characteristics with the patients with diabetes. Overall, a higher HbA1c concentration was strongly associated with CKD or CVD after adjustment for traditional risk factors. The patients with known diabetes had a 2-fold higher odds of CKD or CVD. However, when both parameters were introduced in the same model, the HbA1c concentration was only significantly associated with clinical endpoints (OR: 1.4, 95% CI, 1.1-1.6, P = 0.002). An increase in HbA1c of one percentage point was associated with a 30% to 40% increase in the rate of CKD or CVD. This relationship was apparent in persons with and without known diabetes. ROC curves illustrated that a HbA1c of 37 mmol/mol (5.5%) was the optimal value in terms of sensitivity and specificity for predicting endpoints in this population. CONCLUSION: HbA1c levels were associated with a higher prevalence of CKD and CVD cross-sectionally, regardless of diabetes status. These data support the value of HbA1c as a marker of cardiovascular and renal disease in the general population.

Frequency of Fabry disease in male and female haemodialysis patients in Spain

BACKGROUND: Fabry disease (FD), an X-linked lysosomal storage disorder, is caused by a reduced activity of the lysosomal enzyme alpha-galactosidase A. The disorder ultimately leads to organ damage (including renal failure) in males and females. However, heterozygous females usually present a milder phenotype with a later onset and a slower progression. METHODS: A combined enzymatic and genetic strategy was used, measuring the activity of alpha-galactosidase A and genotyping the alpha-galactosidase A gene (GLA) in dried blood samples (DBS) of 911 patients undergoing haemodialysis in centers across Spain. RESULTS: GLA alterations were found in seven unrelated patients (4 males and 3 females). Two novel mutations (p.Gly346AlafsX347 and p.Val199GlyfsX203) were identified as well as a previously described mutation, R118C. The R118C mutation was present in 60% of unrelated patients with GLA causal mutations. The D313Y alteration, considered by some authors as a pseudo-deficiency allele, was also found in two out of seven patients. CONCLUSIONS: Excluding the controversial D313Y alteration, FD presents a frequency of one in 182 individuals (0.55%) within this population of males and females undergoing haemodialysis. Moreover, our findings suggest that a number of patients with unexplained and atypical symptoms of renal disease may have FD. Screening programmes for FD in populations of individuals presenting severe kidney dysfunction, cardiac alterations or cerebrovascular disease may lead to the diagnosis of FD in those patients, the study of their families and eventually the implementation of a specific therapy.

Guidelines for specialized nutritional and metabolic support in the critically-ill patient. Update. Consensus SEMICYUC-SENPE: Acute renal failure

Nutritional support in acute renal failure must take into account the patient's catabolism and the treatment of the renal failure. Hypermetabolic failure is common in these patients, requiring continuous renal replacement therapy or daily hemodialysis. In patients with normal catabolism (urea nitrogen below 10 g/day) and preserved diuresis, conservative treatment can be attempted. In these patients, relatively hypoproteic nutritional support is essential, using proteins with high biological value and limiting fluid and electrolyte intake according to the patient's individual requirements. Micronutrient intake should be adjusted, the only buffering agent used being bicarbonate. Limitations on fluid, electrolyte and nitrogen intake no longer apply when extrarenal clearance techniques are used but intake of these substances should be modified according to the type of clearance. Depending on their hemofiltration flow, continuous renal replacement systems require high daily nitrogen intake, which can sometimes reach 2.5 g protein/kg. The amount of volume replacement can induce energy overload and therefore the use of glucose-free replacement fluids and glucose-free dialysis or a glucose concentration of 1 g/L, with bicarbonate as a buffer, is recommended. Monitoring of electrolyte levels (especially those of phosphorus, potassium and magnesium) and of micronutrients is essential and administration of these substances should be individually-tailored.

Resistencia de la hiperhomocisteinemia del paciente renal al tratamiento con dosis suprafisiológicas de ácido fólico parenteral

Hemodialysis patients present an increase in plasma homocysteine (Hcy) due to methylation impairment caused by uremia and the deficiency of the co-factors needed (vitamin B, folic acid). This correlates with a more common development of premature vascular disease. There is no consensus on the therapy, with a poor response to oral administration of conventional doses of folic acid. In this work, we assessed the response of hyperhomocysteinemia in 73 regular hemodialysis patients after the administration of 50 mg of parenteral folinic acid for 18 months. Plasma homocysteine of the patients at the time of the study beginning presented mean values of 22.67 (micromol/L). During the first year of supplementation the mean value was kept at 20 micromol/L. From the first year to the end of the 18-months observation period the mean homocysteine levels were 19.58 micromol/L. Although we found a clear trend towards a decrease in plasma homocysteine levels during the treatment period, there were no significant differences. Homocysteine levels did not come back to normal in none of the patients treated.

Primary renal lymphoma: long-term results of two patients treated with a chemotherapy + rituximab protocol.

Primary renal lymphoma (PRL) is a rare disease of which the etiology and pathogenesis remain controversial, and there is currently no standard treatment for it. We present the results of a long-term followup of two patients who were diagnosed with PRL and treated with cyclophosphamide, adriamycin, vincristine, prednisolone and rituximab (CHOP + R) regimen. Both patients reached a complete response, and there is no evidence of recurrence after 4.5- and 5-year followup periods. Based on our experience and other recently published studies, we recommend the combination of CHOP + rituximab as the elective treatment for this disease. To our knowledge, this is the longest followup period with a complete response that has been reported with this modality of treatment.

Nephron-sparing surgery for adenocarcinoma in a renal allograft.

The incidence of malignant tumors in recipients of renal allografts is higher than in the general population. Renal cell carcinoma (RCC) accounts for 4.6% of the tumors in transplanted patients; of them, only 10% are found in transplanted kidneys. Transplantectomy has always been the usual treatment. However, during the last years, nephron-sparing surgery of the allograft is more frequently done in well-selected cases, and therefore dialysis can be avoided. We report the case of a 37-year-old female patient with renal transplant, diagnosed with a 4.5 cm tumor in the lower pole of the renal allograft. The patient underwent partial nephrectomy successfully. Six years after surgery, there is no evidence of recurrence of the disease and the patient maintains an adequate renal function.

Vertebral fractures in patients with inflammatory bowel disease compared with a healthy population: a prospective case-control study.

BACKGROUND A prospective study was performed to compare the prevalence of morphometric vertebral fractures (MVF) between patients with inflammatory bowel disease (IBD) and healthy subjects and to identify predictive factors of fracture. METHODS A total of 107 patients with IBD (53 with Crohn's disease and 54 with ulcerative colitis) and 51 healthy subjects participated in the study. Information about anthropometric parameters, toxins, previous fractures, and parameters related to this disease were evaluated. The index of vertebral deformity, bone mass density (BMD), and biochemical parameters were calculated. RESULTS A total of 72 fractures were detected in 38.32% of patients with IBD, and 10 fractures were detected in 13.73% of healthy subjects; the risk of fracture in patients with IBD was higher than that in control subjects (OR, 4.03; 95% CI, 1.652-9.847; p < 0.002). We found no correlation between fracture and BMD in patients with IBD (lumbar spine, r = -0.103, p = 0.17 and femoral neck, r = -0.138, p = 0.07). Corticosteroid treatment was not associated with prevalent vertebral fractures nor with taking corticosteroids (r = 0.135, p = 0.14) or the duration for which they were taken (r = 0.08, p = 0.38), whereas this relationship was present in the controls (r = -0.365, p = 0.01). In the multivariate analysis, none of the measured parameters were significantly predictive of fracture, only to manifested IBD. Hypovitaminosis D was observed in 55.14% of patients with IBD. CONCLUSIONS The prevalence of morphometric vertebral fractures is higher in patients with IBD than in the healthy population, without association with BMD or corticoid treatment. Simply having IBD was proven to be a predictive factor of fracture. We observed a high incidence of hypovitaminosis D in patients with IBD.

Angiographic demonstration of neoangiogenesis after intra-arterial infusion of autologous bone marrow mononuclear cells in diabetic patients with critical limb ischemia.

Critical limb ischemia in diabetic patients is associated with high rates of morbidity and mortality. Suboptimal responses to the available medical and surgical treatments are common in these patients, who also demonstrate limited vascular homeostasis. Neovasculogenesis induced by stem cell therapy could be a useful approach for these patients. Neovasculogenesis and clinical improvement were compared at baseline and at 3 and 12 months after autologous bone marrow-derived mononuclear cell (BMMNC) transplantation in diabetic patients with peripheral artery disease. We conducted a prospective study to evaluate the safety and efficacy of intra-arterial administration of autologous BMMNCs (100-400 × 10(6) cells) in 20 diabetic patients with severe below-the-knee arterial ischemia. Although the time course of clinical effects differed among patients, after 12 months of follow-up all patients presented a notable improvement in the Rutherford-Becker classification, the University of Texas diabetic wound scales, and the Ankle-Brachial Index in the target limb. The clinical outcome was consistent with neovasculogenesis, which was assessed at 3 months by digital subtraction angiography and quantified by MetaMorph software. Unfortunately, local cell therapy in the target limb had no beneficial effect on the high mortality rate in these patients. In diabetic patients with critical limb ischemia, intra-arterial perfusion of BMMNCs is a safe procedure that generates a significant increase in the vascular network in ischemic areas and promotes remarkable clinical improvement.

Accumulation of scandium in plasma in patients with chronic renal failure.

Scandium (Sc) is an element with many industrial applications, but relatively little is known about its physiological and/or toxicological effects, and very little data are available concerning the role of Sc in chronic renal failure (CRF). This paper examines the changes in plasma levels of Sc in predialysis patients with CRF and the relationship with blood parameters. The participants in this trial were 48 patients with CRF in predialysis and 53 healthy controls. Erythrocyte, haemoglobin, and haematocrit counts in blood were determined, and levels of creatinine, urea, uric acid, albumin, total protein and Sc were measured in plasma. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault index. The CRF patients were found to have higher plasma levels of creatinine, urea, uric acid, albumin, total protein, and Sc and a lower GFR than that the controls. Scandium in plasma was positively correlated with creatinine and plasma urea and negatively correlated with GFR, haemoglobin, and haematocrit and was associated with the risk of lower levels of erythrocytes, haemoglobin, and haematocrit. CRF was associated with increases in the circulating levels of scandium.

Acetylcholinesterase inhibitors and healing of hip fracture in Alzheimer's disease patients: a retrospective cohort study.

OBJECTIVES This study was designed to assess effects of cholinergic stimulation using acetylcholinesterase inhibitors (AChEIs), a group of drugs that stimulate cholinergic receptors and are used to treat Alzheimer's disease (AD), on healing of hip fractures. METHODS A retrospective cohort study was performed using 46-female AD patients, aged above 75 years, who sustained hip fractures. Study analyses included the first 6-months after hip fracture fixation procedure. Presence of AChEIs was used as predictor variable. Other variables that could affect study outcomes: age, body mass index (BMI), mental state or type of hip fracture, were also included. Radiographic union at fracture site (Hammer index), bone quality (Singh index) and fracture healing complications were recorded as study outcomes. The collected data was analyzed by student's-t, Mann-Whitney-U and chi-square tests. RESULTS No significant differences in age, BMI, mental state or type of hip fracture were observed between AChEIs-users and nonusers. However, AChEIs-users had better radiographic union at the fracture site (relative risk (RR),2.7; 95%confidence interval (CI),0.9-7.8), better bone quality (RR,2.0; 95%CI,1.2-3.3) and fewer healing complications (RR,0.8; 95%CI,0.7-1.0) than nonusers. CONCLUSION In elderly female patients with AD, the use of AChEIs might be associated with an enhanced fracture healing and minimized complications.

The development of anemia is associated to poor prognosis in NKF/KDOQI stage 3 chronic kidney disease

BACKGROUND: Anemia is a common condition in CKD that has been identified as a cardiovascular (CV) risk factor in end-stage renal disease, constituting a predictor of low survival. The aim of this study was to define the onset of anemia of renal origin and its association with the evolution of kidney disease and clinical outcomes in stage 3 CKD (CKD-3). METHODS: This epidemiological, prospective, multicenter, 3-year study included 439 CKD-3 patients. The origin of nephropathy and comorbidity (Charlson score: 3.2) were recorded. The clinical characteristics of patients that developed anemia according to EBPG guidelines were compared with those that did not, followed by multivariate logistic regression, Kaplan-Meier curves and ROC curves to investigate factors associated with the development of renal anemia. RESULTS: During the 36-month follow-up period, 50% reached CKD-4 or 5, and approximately 35% were diagnosed with anemia (85% of renal origin). The probability of developing renal anemia was 0.12, 0.20 and 0.25 at 1, 2 and 3 years, respectively. Patients that developed anemia were mainly men (72% anemic vs. 69% non-anemic). The mean age was 68 vs. 65.5 years and baseline proteinuria was 0.94 vs. 0.62 g/24h (anemic vs. non anemic, respectively). Baseline MDRD values were 36 vs. 40 mL/min and albumin 4.1 vs. 4.3 g/dL; reduction in MDRD was greater in those that developed anemia (6.8 vs. 1.6 mL/min/1.73 m2/3 years). These patients progressed earlier to CKD-4 or 5 (18 vs. 28 months), with a higher proportion of hospitalizations (31 vs. 16%), major CV events (16 vs. 7%), and higher mortality (10 vs. 6.6%) than those without anemia. Multivariate logistic regression indicated a significant association between baseline hemoglobin (OR=0.35; 95% CI: 0.24-0.28), glomerular filtration rate (OR=0.96; 95% CI: 0.93-0.99), female (OR=0.19; 95% CI: 0.10-0.40) and the development of renal anemia. CONCLUSIONS: Renal anemia is associated with a more rapid evolution to CKD-4, and a higher risk of CV events and hospitalization in non-dialysis-dependent CKD patients. This suggests that special attention should be paid to anemic CKD-3 patients.

Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms.

BACKGROUND/OBJECTIVES Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old) and old (24 months old) rats. METHODS/FINDINGS Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA) as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA), as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations. CONCLUSIONS The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease) associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.