Aleix Cases

Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases

Summary. From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The median survival was 20 months and six patients survived for > 3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long‐term survivors.

Mspl identifies a biallelic polymorphism in the promoter region of the α2A‐adrenergic receptor gene

Candidate gene: An increased activity of the sympathetic nervous system has been suggested to play a role in the pathophysiology of essential hypertension ( EHT). However, plasma catecholamine levels are not increased in these patients. An increased density of a,,-adrenergic receptors (a,,-AR) has been reported in patients with EHT (Mores et al. 1990, Calls et al. 1995). The activation of these receptors by epinephrine or norepinephrine promotes peripheral vasoconstriction and salt and water retention. The human cc,,-AR gene is located at 10q23-q25. The complete nucleotide sequence of this gene (HUMADRA2R) has been previously published (Fraser et al. 1989), and two restriction fragment length polymorphisms (DraI and Bsu36I RFLPs) have been reported to date (Hoehe et al. 1988, Sun et al. 1992). A significant association between DraI RFLP and essential hypertension has been described (Lockette et al. 1995, Svetkey et al. 1996), although there is no general agreement on these findings.

Tumor Markers in Chronic Renal Failure and Hemodialysis Patients

Serum levels and the incidence of elevated levels of several tumor markers were measured in 30 patients with chronic renal failure (CRF) of different degrees, as well as in 36 hemodialyzed (HD) patients without clinical evidence of neoplasia. The tumor markers evaluated were carcinoembryonic antigen (CEA), CA 125, CA 15.3, CA 19.9, CA 50, alpha-fetoprotein, neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), prostatic acid phosphatase and prostatic-specific antigen. Serum levels of CEA were above the cutoff limit in 33% of patients with CRF and 47% of HD patients, CA 50 was higher than normal values in 37 and 44% of patients, respectively. SCC was elevated in 43 and 72% of patients, respectively. Serum levels of CA 125 were elevated in 18% of patients with CRF and NSE in 36% of HD patients. In CRF several tumor markers (CEA, SCC, CA 50 and NSE) show a high false positive rate and may be unreliable for monitoring malignancies in uremic patients, while the other markers evaluated appear to maintain their specificity in this situation.

Baseline characteristics of patients with chronic kidney disease stage 3 and stage 4 in spain: the MERENA observational cohort study

BackgroundTo obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD).MethodsMulticenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula.ResultsIn the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels.ConclusionThis study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System.

Visceral Involvement of Dialysis Amyloidosis

Carpal tunnel syndrome, peripheral arthropathy, erosive spondyloarthropathy and lytic bone lesions have all been associated with dialysis amyloidosis. Recent studies indicate that beta 2-microglobulin is the major constituent protein in this new form of amyloidosis. Dialysis amyloidosis was reported to have a local rather than a systemic involvement, although its full extent is yet to be determined. We investigated 3 patients on maintenance hemodialysis with bilateral carpal tunnel syndrome and amyloid arthropathy and found amyloid depositions in several organs. These findings suggest that, in contrast to what had been thought previously, dialysis amyloidosis could have systemic as well as visceral distribution. The amyloid deposits found were resistant against potassium permanganate treatment and reacted with anti-human beta 2-microglobulin antibody.

Effect of recombinant human erythropoietin treatment on circulating reticulated platelets in uremic patients: Association with early improvement in platelet function

Recombinant human erythropoietin improves platelet function in uremia through the correction of anemia, but this effect can be seen also before the hematocrit rise. We studied 12 hemodialyzed patients (seven men, five women) who received recombinant human erythropoietin (40 IU kg−1 i.v., three times weekly) and were evaluated before treatment and after three doses; 24 control subjects were used. Platelet aggregation induced by adenosine 5′‐diphosphate (ADP), epinephrine, collagen, arachidonic acid, and ristocetin, and reticulated platelets determined by flow cytometry after staining with thiazole orange were measured. Platelet aggregation induced by all the agonists were impaired in uremic patients (P < 0.01), but ADP and ristocetin‐induced aggregations improved after treatment (P < 0.01). Hemodialyzed patients had less reticulated platelets than controls (P < 0.01). Reticulated platelets increased after three doses of treatment (P < 0.01). In conclusion, improvement of platelet function at early stages of recombinant human erythropoietin treatment may be attributed to the increase in young platelets detected as reticulated platelets. Am. J. Hematol. 59:105–109, 1998.

TLR4 and NALP3 inflammasome in the development of endothelial dysfunction in uraemia

The increased cardiovascular risk present in chronic kidney disease (CKD) is related to the development of endothelial dysfunction, whose mechanisms are still unclear. Accumulation of toxins and proinflammatory cytokines may constitute danger‐associated molecular patterns (DAMP) to which endothelial cells are continuously exposed. Potential involvement of mechanisms recognizing DAMP, such as TLR and inflammasomes, has been explored.

Nocturnal, every-other-day, online haemodiafiltration: an effective therapeutic alternative

BACKGROUND Longer and more frequent dialysis sessions have demonstrated excellent survival and clinical advantages, while online haemodiafiltration (OL-HDF) provides the most efficient form of dialysis treatment. The aim of this study was to evaluate the beneficial effects of a longer (nocturnal) and more frequent (every-other-day) dialysis schedule with OL-HDF at the same or the highest convective volume. METHODS This prospective, in-centre crossover study was carried out in 26 patients, 18 males and 8 females, 49.2±14 years old, on 4-5 h thrice-weekly post-dilution OL-HDF, switched to nocturnal every-other-day OL-HDF. Patient inclusion criteria consisted of stable patients with good vascular access and with good prospects for improved occupational, psychological and social rehabilitation. Patients were randomly assigned into two groups: Group A received the same convective volume as previously for 6 months followed by a higher convective volume for a further 6 months, while Group B received the same schedule in reverse order. RESULTS Nocturnal every-other-day OL-HDF was well tolerated and 56% of patients who were working during the baseline period continued to work throughout the study with practically no absenteeism. The convective volume was 26.7±2 L at baseline, 27.5±2 with the unchanged volume and 42.9±4 L with the higher volume. eKt/V increased from 1.75±0.4 to 3.37±0.9. Bicarbonate, blood urea nitrogen (BUN) and creatinine values decreased, while phosphate levels fell markedly with a 90% reduction in phosphate binders. Blood pressure and left ventricular hypertrophy (LVH) improved and the use of anti-hypertensive drugs decreased. In both groups, BUN, creatinine and β2-microglobulin reduction ratios improved. Different removal patterns were observed for myoglobin, prolactin and α1-acid glycoprotein. CONCLUSIONS Nocturnal every-other-day OL-HDF could be an excellent therapeutic alternative since good tolerance and occupational rehabilitation, marked improvement in dialysis dose, nutritional status, LVH, phosphate and hypertension control and a substantial reduction in drug requirements were observed. In this crossover study, different removal patterns of large solutes were identified.

Ocular and Auditory Toxicity in Hemodialyzed Patients Receiving Desferrioxamine

During an 18-month period of study 41 hemodialyzed patients receiving desferrioxamine (10-40 mg/kg BW/3 times weekly) for the first time were monitored for detection of audiovisual toxicity. 6 patients presented clinical symptoms of visual or auditory toxicity. Moreover, detailed ophthalmologic and audiologic studies disclosed abnormalities in 7 more asymptomatic patients. Visual toxicity was of retinal origin and was characterized by a tritan-type dyschromatopsy, sometimes associated with a loss of visual acuity and pigmentary retinal deposits. Auditory toxicity was characterized by a mid- to high-frequency neurosensorial hearing loss and the lesion was of the cochlear type. Desferrioxamine withdrawal resulted in a complete recovery of visual function in 1 patient and partial recovery in 3, and a complete reversal of hearing loss in 3 patients and partial recovery in 3. This toxicity appeared in patients receiving the higher doses of desferrioxamine or coincided with the normalization of ferritin or aluminium serum levels. The data indicate that audiovisual toxicity is not an infrequent complication in hemodialyzed patients receiving desferrioxamine. Periodical audiovisual monitoring should be performed on hemodialyzed patients receiving the drug in order to detect adverse effects as early as possible.

Tratamiento eficaz de la arteriolopatía urémica calcificante con bifosfonatos

BACKGROUND AND OBJECTIVES Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare but life-threatening condition that almost exclusively affects patients with chronic kidney disease. Several therapies have been employed to treat this disease but with irregular results. We report a prospective case series of eight patients diagnosed with CUA in our unit between 2002 and 2010. MATERIAL AND METHOD The series consisted of eight patients with CUA (including 4 men, 5 dialysis patients and 3 with functioning allografts) who were treated with bisphosphonates. The diagnosis was by clinical suspicion and a confirmatory biopsy. Five patients had a previous history of high calcium-phosphorus product, 6 had a history of high parathyroid hormone levels (>800pg/ml), 4 had undergone parathyroidectomy, 5 had a history of high cumulative doses of steroids, and 6 patients were under dicoumarin treatment. None of the patients were obese or had diabetes mellitus. RESULTS In all patients, progression of skin lesions stopped between 2 to 4 weeks after starting bisphosphonate therapy, with no changes in blood levels of calcium and phosphate. Improvement in pain and lesions was faster in patients receiving intravenous ibandronate. All of these patients remained on bisphosphonate treatment for at least 6 months until the wounds healed completely. No recurrences have been observed after follow-up periods between 1 and 9 years. Renal function remained stable in transplant recipients. The treatment was well tolerated and no adverse effects were observed. CONCLUSIONS Bisphosphonates could be a new and attractive alternative to treat CUA.