COVID-19 vaccination among Spanish nephrologists: Acceptance and side effects.

INTRODUCTION: Four vaccines against Covid-19 have been approved to date. Their acceptance and safety have not been addressed on healthcare workers. The aim of the present study is to evaluate vaccination rates and side effects among Spanish nephrologists. METHODS: All the Spanish nephrologists were invited to participate in this survey. Data on demographics, Covid-19 infection status, received vaccine doses and side effects were collected. Acceptance and side effects were analyzed for Covid-19 vaccination. Factors associated to vaccination were assessed and a multivariate adjusted model was constructed to determine independent predictors for Covid-19 vaccine side effects. RESULTS: A total of 708 nephrologists answered the survey (460 [65%] women, mean age 44±11 years). Six-hundred and eight (86%) had received the first dose and 513 (72%) were fully vaccinated. Most of the subjects (565, 93%) received BNT162b2 (Pfizer-BioNTech®) vaccine. Among vaccinated nephrologists, 453 (75%) presented any side effect; the most frequent was local reaction (68%), followed by myalgia (44%), tiredness (39%) and headache (34%). Age (OR 0.97, 95%CI [0.95-0.99], p<0.0001) and prior Covid-19 infection (OR 2.37, 95%CI [1.27-4.42], p=0.007) were independent predictors for developing side effects with Covid-19 vaccine. Overall side effects were similar with both vaccines, being myalgia (p=0.006) and tiredness (p=0.032) more frequent with the Pfizer-BioNTech® one. CONCLUSION: Age and prior Covid-19 infection were predictors of vaccination side effects among Spanish nephrologists.

Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

INTRODUCTION: 25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. AIMS: To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. METHODS: Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. RESULTS: At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. CONCLUSIONS: Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators.

[Have we forgotten the most important thing to prevent bacteremias associated with tunneled hemodialysis catheters?]. / ¿Hemos olvidado lo más importante para prevenirlas bacteriemias en pacientes portadores de catéterespara hemodiálisis?

Bacteremia associated with tunneled central venous catheters (CVC) is a major complication in hemodialysis patients. Strategies that aim to prevent catheter-related bacteremia (CRB), ranging from the application of topical antibiotics to the use of different catheter-lock solutions, have been studied, but limited interest has been shown about following standardization of aseptic care and maintenance of CVC by experienced staff. This study reports CRB incidence obtained with a strict infection prophylaxis protocol based on universal precautions against infection adopted in our Unit by qualified nursing hemodialysis staff. During a period of 20 months, 32 patients received 42 CVC. There were 2 CRB, with an incidence of 0.24 CRB/1000 days-catheter. This study shows that an optimal catheter-use management reduces the incidence of CRB to excellent rates. The use of a protocol directed to vigorously protect the catheter at the time of usage by specialized teams is critically important and is highly recommended.

Early steroid treatment improves the recovery of renal function in patients with drug-induced acute interstitial nephritis.

The role of steroid treatment in drug-induced acute interstitial nephritis (DI-AIN) is controversial. We performed a multicenter retrospective study to determine the influence of steroids in 61 patients with biopsy-proven DI-AIN, 52 of whom were treated with steroids. The responsible drugs were antibiotics (56%), non-steroidal anti-inflammatory drugs (37%) or other drugs. The final serum creatinine was significantly lower in treated patients while almost half of untreated patients remained on chronic dialysis. Among treated patients, over half showed a complete recovery of baseline renal function, whereas the rest remained in renal failure. There were no significant initial differences between these two subgroups in terms of duration or dosage of steroids. After withdrawal of the presumed causative drug, we found that when steroid treatment was delayed (by an average of 34 days) renal function did not return to baseline levels compared to those who received steroid treatment within the first 2 weeks after withdrawal of the offending agent. We found a significant correlation between the delay in steroid treatment and the final serum creatinine. Renal biopsies, including three patients who underwent a second biopsy, showed a progression of interstitial fibrosis related to the delay in steroid treatment. Our study shows that steroids should be started promptly after diagnosis of DI-AIN to avoid subsequent interstitial fibrosis and an incomplete recovery of renal function.

Role of haemodialysis and hepatitis c virus infection in spontaneous and induced cytokine production of patients with chronic renal disease.

Cytokines modulate general and virus infection-related host immune responses. We have investigated cytokine responses in chronic renal disease patients with regard to haemodialysis and hepatitis C virus (HCV) infection. Compared with healthy subjects with normal renal function (n=15), non-dialyzed/renal disease individuals without HCV infection (n=11) showed increased production of tumour necrosis factor (TNF)-alpha, interleukin (IL-)6, IL-10, interferon (IFN-)gamma and IL-12 by blood mononuclear cells (P<0.05). These inflammatory cytokine responses were abolished in haemodialysis patients (n=37;P<0.05), except for IL-12. This hyporesponsiveness in haemodialysis patients was more evident in stimulatory conditions, as shown by the consistent inhibition of IFN-gamma production, and the failure of exogenous IFN-gamma to prime for IL-12 inducibility (P<0.01). The disturbed cytokine response appeared to focus in the T-helper lymphocyte phenotype 1 (Th(1)) because the stimulation of IL-6 and IL-10 (Th(2)phenotype cytokines) was not impaired. The pattern of response was similar among haemodialysis patients with (n=24) or without (n=13) HCV infection. However, HCV-positive haemodialysis patients had a blunted TNF-alpha response (P<0.05) and failed to increase the stimulated IFN-gamma and IL-12 production (P<0.01) compared with chronic hepatitis C patients without renal disease (n=25). On the contrary, IL-10 stimulation was higher in HCV-positive haemodialysis patients (P<0.01). These results disclose the presence in haemodialysis patients of markedly abnormal general and HCV infection-related cytokine responses; the inhibitory alterations appear to affect predominantly the stimulated responses via the Th(1)subset and its relationship with monocyte response with possible pathogenic and therapeutic implications.

GBV-C/HGV-RNA in serum and peripheral blood mononuclear cells in hemodialysis patients.

BACKGROUND: Hemodialysis patients are at high risk of hepatitis B, C, and G virus infection. The prevalence of GBV-C/HGV-RNA was analyzed in serum and peripheral blood mononuclear cells (PBMCs) from 52 hemodialysis patients. METHODS: GBV-C/HGV-RNA detection was performed by reverse transcription-polymerase chain reaction (RT-PCR) with primers of 5'-noncoding (5'-NC) and NS3 regions of the GBV-C/HGV genome. To increase sensitivity, serum samples were ultracentrifuged prior to the RT-PCR to concentrate the viral particles. The amplified products from 20 serum and 5 peripheral blood mononuclear cells (PBMC) samples were sequenced. RESULTS: GBV-C/HGV-RNA was detected in sera of 9 (17%) and in PBMCs of 30 (58%) patients. After serum ultracentrifugation, GBV-C/HGV-RNA was positive in 20 (95%) of the patients, with GBV-C/HGV-RNA only in PBMCs. Thus, GBV-C/HGV-RNA was detected in serum and PBMCs from 29 (56%) patients, four of whom had antibodies against GBV-C/HGV E2 protein (anti-HGE2); one patient (2%) had GBV-C/HGV-RNA only in PBMCs, but was anti-HGE2 positive. Seven (32%) patients who did not have GBV-C/HGV-RNA were anti-HGE2 positive. The nucleotide sequence homology between serum samples from the patients who were GBV-C/HGV-RNA positive after ultracentrifugation, and paired serum and PBMCs from five of them, ranged from 90 to 96% and from 92 to 98%, respectively. CONCLUSIONS: We found a high prevalence of GBV-C/HGV-RNA in serum and PBMC samples from hemodialysis patients. Whether or not this finding can be extended to other populations requires further study.

Role of cytokines in the response to erythropoietin in hemodialysis patients.

BACKGROUND: Cytokines are regulatory factors of erythropoiesis, especially in pathologic conditions. Even though a relevant role for a deranged cytokine production in the pathogenesis of dialysis anemia has been suggested, no data are available that analyze the role of cytokines in the key therapeutic issue of the needs of erythropoietin. The aim of the present study in hemodialysis patients was, therefore, to examine the relationship between the dose of recombinant human erythropoietin (EPO) and the production of cytokines by peripheral blood mononuclear cells (PBMC). METHODS: After the exclusion of subjects with major active causes of EPO resistance, data from 34 hemodialysis patients were available for analysis. Cytokine levels were measured in the supernatants of stimulated [with bacterial lipopolysaccharide and interferon gamma (IFN-gamma)] and unstimulated PBMC. Mean yearly values of hematocrit, hemoglobin, transferrin saturation, ferritin, parathormone (PTH) and aluminum levels and EPO doses (U/kg/week) were calculated. For analysis, the 34 patients were divided according to their cutoff requirements for EPO: patients with requirements of EPO > or = 60 U/kg/week (group A1, 26 subjects) versus EPO < 60 U/kg/week (group B1, 8 subjects) and patients with requirements of EPO > or = 100 U/kg/week (group A2, 18 subjects) versus <100 U/kg/week (group B2, 16 subjects). RESULTS: A significant direct correlation between interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-a) production values and EPO doses was found (P = 0.039 and P = 0.02 respectively). On the other hand, there was a significantly negative correlation between interleukin-12 (IL-12) production values and EPO doses (P = 0.029). Patients of groups A1 and A2 had spontaneously higher tumor necrosis factor-alpha (TNF-alpha) and lower IL-12 and IFNgamma production compared to patients from groups B1 and B2. CONCLUSIONS: Our data disclose a previously undescribed pattern of cytokine alteration that is relevant to determine increased needs of EPO in hemodialysis patients. The present results have potential applicability in designing strategies to improve EPO resistance.

Hepatitis B virus DNA in serum and blood cells of hepatitis B surface antigen-negative hemodialysis patients and staff.

Patients undergoing chronic hemodialysis, as well as dialysis staff members, are at high risk of infection with hepatitis B virus (HBV). We have analyzed by PCR the presence of HBV DNA in serum and peripheral blood mononuclear cells (PBMC) from 33 hepatitis B surface antigen (HBsAg)-negative hemodialysis patients and 24 dialysis unit staff members; eight of the 24 staff members had an acute hepatitis B resolved 13 to 21 yr before. HBV DNA was detected in serum of 19 (58%) patients (12 of 17 with and 7 of 16 without anti-HBV antibodies). HBV DNA was found in PBMC of 18 (54%) patients (13 of 17 with and 5 of 16 without anti-HBV antibodies). In the staff members, serum HBV DNA was found only in the individuals who suffered a previous acute hepatitis (P < 0.005). HBV DNA was detected in PBMC of four of six staff members (all with previous acute hepatitis). In two HBV DNA-positive PBMC samples, viral RNA was detected by reverse transcription-PCR. To ascertain whether the HBV DNA detected in serum was encapsulated, seven HBV DNA-positive serum samples were digested with DNase before PCR. After treatment, HBV DNA remained detectable in four cases. In conclusion, HBV DNA in serum and PBMC is detectable in a high proportion of HBsAg-negative hemodialysis patients and may persist several years after a resolved acute hepatitis B. The viral DNA is encapsulated and remains transcriptionally active in PBMC. In the anti-HBs-negative patients, HBV DNA is, at the present time, the only means for diagnosing a past HBV hepatitis.

[Diagnosis of renovascular disease by heart catheterization]. / Diagnóstico de enfermedad renovascular mediante cateterismo cardíaco.

Atherosclerotic renovascular disease is a common entity, particularly in persons older than 50 years of age and especially in those patients with other evidence of atherosclerotic vascular disease. The illness clearly progresses in some patients, and progression rate appears to be highly variable. Taken into account the apparent high prevalence of renovascular disease in older persons, it is possible that this disorder be the cause of end stage renal disease in 5% to 15% of patients currently entering the dialysis program each year. Surgery and percutaneous angioplasty can both improve renal function in patients with renal artery stenosis. We describe a patient in whom the detection of renovascular disease was made accidentally at the time of coronary arteriography. He presented an acute renal failure after use of angiotensin-converting enzyme inhibitors and/or contrast media associated nephrotoxicity, and was treated with percutaneous transluminal balloon angioplasty and had a successful outcome.

Concentrated ascitic fluid reinfusion in cirrhotic patients: a simplified method.

A new method for ascites filtration and reinfusion, which uses a single Cuprophan filter and is performed in the dialysis unit, is reported. Thirty-one procedures were performed in 17 patients with cirrhosis and massive ascites. A mean volume of 8.6 L of ascitic fluid was removed; from this volume, 5 L were ultrafiltered and a concentrated ascitic fluid was reinfused (x = 359.8 mL). The whole procedure was completed in a mean time of 248 minutes. No relevant method-related complications were detected. Moreover, no significant changes in blood urea nitrogen (BUN), creatinine, plasma and urinary electrolytes, or platelet count were found, even in the case of repeated procedures (two to nine times). The reinfused fluid contained a mean value of albumin of 4.7 g/dL and significant amounts of globulins and complement. The overall cost of the materials used in the procedure ($49.46) offered competitive advantages with respect to other types of frequently used methods. In conclusion, we present a safe, effective, and time- and cost-saving technique for ascites reinfusion that represents an advantageous alternative to more complicated and expensive methods or to the currently used medical therapy.

Undiagnosed hepatitis C virus infection in hemodialysis patients: value of HCV RNA and liver enzyme levels.

At present, routine screening for hepatitis C virus (HCV) infection is based on the detection of antiviral antibodies. Underdiagnosis of HCV infection by using HCV antibody tests, however, still occurs. Additional diagnostic means are provided by the polymerase chain reaction (PCR). The measurement of aminotransferase (ASAT and ALAT) has served as an auxiliary, less specific test. The present research aimed to design practical and low cost strategies to diminish underdiagnosis of HCV infection in dialysis patients. With this purpose in mind, we examined whether aminotransferases values in HCV antibody-negative patients could be related to undiagnosed HCV infection, by using HCV RNA testing by PCR as the gold standard. In 112 hemodialysis patients, we found 78 negative and 34 positive for HCV antibodies. A major finding was that 222 (28.2%) out of the 78 HCV antibodies-negative patients had positive HCV RNA by PCR. In repeated samples taken at six months follow-up from 19 out of these 22 patients, only one of them was positive for anti-HCV antibodies; moreover, a positive HCV RNA by PCR was confirmed in 13 (68.5%) of them. Within the HCV antibody-negative group, the mean values of ASAT, ALAT and gammaglutamiltransferase were higher (P < 0.001, P < 0.001 and P < 0.02, respectively) in the HCV PCR-positive versus the HCV PCR-negative patients. No significant differences were found in the liver enzyme values between the HCV antibody-negative, HCV RNA positive and the HCV antibody positive, HCV RNA positive individuals. Histological samples from two HCV RNA positive, HCV antibody-negative patients disclosed the presence of a mild liver disease. In conclusion, the present study demonstrates the critical importance of HCV RNA determination by PCR in hemodialysis patients who have no detectable circulating antibodies against the HCV. Furthermore, in conditions in which PCR technology is not readily available, we have established that the existence of a moderate increase of aminotransferases is a helpful clue to detect patients with absent HCV antibodies, and might represent an useful, low cost tool for HCV screening in dialysis patients.

Acute renal failure due to sulphadiazine crystalluria in AIDS patients.

We report two AIDS patients who developed acute renal failure while receiving sulphadiazine for cerebral toxoplasmosis. Renal ultrasound revealed diffuse bilateral echogenic shadowing material. 'Sheaves of wheat' crystals, typical of sulphadiazine crystalluria, were present in the urine. One patient required a percutaneous nephrostomy. Hydration and urine alkalinisation resulted in rapid improvement of renal function and ultrasonographic findings. Sulphadiazine-induced crystalluria and acute renal failure is increasingly frequent. Awareness of its existence may lead to prevention and early conservative treatment.

Relationships between plasma ferritin and aminotransferase profile in haemodialysis patients with hepatitis C virus.

BACKGROUND: HCV infection is a major complication among patients undergoing dialysis therapy throughout the world. In the years prior to the use of human recombinant erythropoietin (rHuEpo), patients undergoing haemodialysis were subjected to an excessive iron load as a consequence of frequent blood transfusions. Recent data in the non-dialysis population have shown a positive correlation between iron deposits and the severity of HCV hepatitis and between iron deposition and an impaired response to interferon therapy. METHODS: One hundred and five haemodialysis patients were studied. Every patient was screened for HCV infection by ELISA II and HCV RNA. Serum biochemistries were analysed by SMAC20. Ferritin was measured by radioimmunoassay. RESULTS: The aminotransferase levels for the HCV positive (n = 39) and negative patients (n = 66) were below the normal levels for the general population. The mean values of aminotransferases and plasma ferritin were, however, higher in the HCV-positive patients than in the HCV-negative patients. A positive correlation between aminotransferases and plasma ferritin was evident in HCV-positive patients, which was absent in the HCV-negative individuals. The histological severity of liver disease (n = 7) was, however, not statistically related with the levels of either ferritin or aminotransferases. CONCLUSION: HCV infection is a relevant variable when estimating iron deposits by measuring plasma ferritin. Accordingly, a misinterpretation of the actual amount of iron deposits may occur in HCV-positive patients, which should be taken into account at the time of planning their iron reposition therapy. On the other hand, the level of iron deposits might have a significant role in the evolution of HCV-related liver disease.