Predictors of nutritional and inflammation risk in hemodialysis patients.

BACKGROUND: Malnutrition and chronic inflammation are prevalent complications in hemodialysis (HD) patients. Different nutritional assessment tools are used to identify patients at risk. A composite and comprehensive malnutrition inflammation score (MIS) has been correlated with morbidity and mortality, and appears to be a robust and quantitative tool. OBJECTIVES: Determine malnutrition risk profile in a sample of portuguese HD patients; determine the association of clinical and laboratory factors with MIS, and the impact of each parameter on MIS. METHODS AND RESULTS: We performed, between September 15th of 2015 and January 31st of 2016, a cross sectional analysis of 2975 patients, representing 25% of portuguese HD patients. 59% were men (66.7 ± 14.8 years); 31% diabetic; 79% and 21% performed, respectively, high-flux HD and HDF. A MIS >5 was considered to indicate higher risk and was present in 1489 patients (50%). Amongst all parameters, comorbilities/dialysis vintage, transferrin, functional capacity, changes in body weight and decreased fat stores showed the higher impact, while albumin had one of the lowest impact on the nutritional risk. MULTIVARIABLE ANALYSIS: Higher age (>75 years, OR 1.71, p < 0.001), diabetes (OR 1.25, p = 0.026), lower P levels (OR 1.57,p = 0.001), higher Ca levels (OR 1.51, p < 0.001), higher ERI (OR 1.05, p < 0.001), higher Kt/V (OR 2.14, p < 0.001) and higher CRP (OR 1.01, p < 0.001) were independently associated with a higher risk of MIS>5; higher nPNA (OR 0.29, p < 0.001) and higher Pcreat (OR 0.88, p < 0.001) were associated with a risk reduction of MIS>5 (95% CI). CONCLUSIONS: Routine clinical and analytic parameters were found to be associated with MIS range that might indicate higher risk, and may represent a simple alert sign for the need of further assessments.

Intravenous Immunoglobulin and Rituximab in HLA Highly Sensitized Kidney Transplant Recipients.

INTRODUCTION: HLA-sensitized patients are penalized both in the access to kidney transplantation (KT) and, once transplanted, in the incidence of rejections and long-term allograft survival despite aggressive induction and maintenance therapy. METHODS: This study retrospectively evaluates the impact of combining T- and B-cell-depleting agents and intravenous immunoglobulin for induction therapy in 45 highly sensitized KT patients (anti-panel reactive antibodies >60%, positive flow cytometry crossmatch or donor specific antibodies at the time of transplantation). The outcome data included the occurrence of biopsy-proven acute rejection, new-onset proteinuria, development of leukopenia, incidence of poliomavirus infection (BK or JC virus), fungal or bacterial infection after KT, de novo neoplasia, graft function, graft loss, or death with functioning KT. RESULTS: The average panel reactive antibody was 62.5%; 41 patients (91.1%) had ≥3 HLA mismatches with the donor and 91.1% of patients had class I or II anti-HLA antibodies. Fourteen patients (31.1%) presented pre-KT donor-specific antibodies and 6 patients (13.3%) had a positive flow cytometry cross-match at the time of transplantation. The incidence of acute rejection in the first 6 months was 24.4% and the cumulative incidence was 37.8%. Two patients were diagnosed with leukopenia in the first 6 months after KT. Two patients (4.5%) had cytomegalovirus disease, 17 patients (37.8%) were diagnosed with bacterial infections. Cutaneous neoplasms were identified in 5 patients (11.1%) and solid tumors in 4 (8.9%). The death-censored graft survival was 100% in the first 6 months and 93.5% at the last evaluation. Patient survival in the same periods was 97.8% and 93.3%, respectively. CONCLUSIONS: Induction immunosuppressive therapy with intravenous immunoglobulin and rituximab is effective; outcomes demonstrate an excellent patient and allograft survival and allograft function over the follow-up period.

Hepatitis C Virus Eradication in Kidney Transplant Recipients: A Single-Center Experience in Portugal.

INTRODUCTION: Hepatitis C (HCV) is a major cause of liver impairment post-kidney transplantation (KT). Anti-HCV direct-acting antivirals (DAA) made viral eradication possible. METHODS: We performed a retrospective review of KT patients (n = 23) who received DAA at our hospital. Sustained viral response (SVR) was defined as absence of viral detection 12 weeks after cessation of therapy. RESULTS: From 1985 to September 2017, 1440 patients underwent transplantation at Hospital Santa Cruz. From a total of 32 HCV RNA+ KT recipients on follow-up, we describe the first 23 patients treated with DAA. They were 56.7 ± 9.1 years old; 22 were white, 52.2% were males, they underwent transplantation 18.8 ± 9.0 years ago, and 13 had genotype 1B, 21 were naïve, and 9 had stages F3/F4. All but 2 patients, treated with grazoprevir/elbasvir, received sofosbuvir (18 with ledispasvir, 2 with daclastavir, and 4 with simultaneous ribavirin). Pretreatment, intra-treatment, and post-treatment creatinine clearances were 61.4, 60.6, and 60.7 mL/min/1.73 m2, respectively (not significant [NS]). Cyclosporine A was the basis of immunosuppression in the majority [(n = 14); pretreatment and intra-treatment levels were 79.5 ± 23.0 and 91.8 ± 26.0 ng/mL, respectively (P = .08)]; tacrolimus (n = 8) and mammalian target of rapamycin (mTOR) levels (n = 5) were also similar. One patient interrupted ribavirin after 7 weeks due to anemia; all other patients completed the treatment course without major side effects. Only 3 patients presented positive viral RNA at the fourth week of treatment and SVR was achieved in 100% of the patients 12 weeks after treatment. CONCLUSIONS: DAA therapy was well tolerated and effective in 100% of our treated patients, without significant impact on the renal function or on the immunosuppression.

HCV-infected Renal Transplant Recipients: Our Experience before the Availability of New Antiviral Drugs.

BACKGROUND: Natural history of HCV-infected renal transplant recipients is about to change with the invention of new drugs available for the treatment of HCV. OBJECTIVE: To analyze the evolution of renal transplant recipients infected with HCV in 30 years of activity of a Renal Transplantation Unit. METHODS: We studied 1334 patients who underwent renal transplantation between 1985 and 2015. RESULTS: 189 (14.2%) of these 1334 were found HCV seropositive. 60 were HCV RNA-positive for >6 months. 5 died with a functioning graft; 19 lost their graft and resumed dialysis. Most of the rejections occurred within the first year of the transplantation and none resulted in immediate loss of the graft. In post-transplantation period, 14 patients developed clinical hepatic disease, 10 manifested new-onset diabetes after transplantation, and 4 had de novo neoplasia, none of them had hepatocellular carcinoma. The outcomes of the different variables analyzed were similar between patients with HCV-infection and those with HCV and HBV co-infection. The median survival time was 13.4 (95% CI: 10.7-16.1) years; the median survival time of patients without HCV infection was 14.6 (95% CI: 13.8-15.4) years (p=0.23). CONCLUSION: In the era before the availability of new anti-HCV drugs, our experience with HCV-infected renal transplant recipients revealed similar post-transplantation complications, graft and patient survival as those not infected with HCV.

Cortical bone analysis in a predialysis population: a comparison with a dialysis population.

This study was designed to characterize cortical bone by histomorphometry in a predialysis population, to correlate turnover, mineralization, and volume between cortical and trabecular bone, and to compare the findings with those in patients treated with maintenance dialysis. We evaluated cortical bone by histomorphometry in 16 patients with stage 3 or stage 4 chronic kidney disease and in 16 dialysis patients. Dual-energy X-ray absorptiometry (DXA) of the distal end of the forearm was performed in seven predialysis patients, and the findings correlated with histologic parameters. Predialysis patients compared with dialysis patients showed increased cortical bone thickness (p = 0.027) and decreased osteonal bone formation rate (p = 0.020) and adjusted apposition rate (p = 0.018), mainly for external cortical bone. In this predialysis population, trabecular bone volume positively correlated with external cortical porosity (r = 0.723, p = 0.003), external cortical thickness (r = 0.569, p = 0.034), and external osteonal accumulation (osteonal osteoid thickness, r = 0.530, p = 0.05; osteonal osteoid volume to bone volume ratio, r = 0.921, p < 0.001; and osteonal osteoid surface to bone surface ratio, r = 0.631, p = 0.016). These correlations were not observed in the internal cortical bone. Cortical osteonal mineralization surface negatively correlated with DXA Z and T scores and bone mineral density for the distal end of the forearm. The osteonal bone formation rate of both internal cortical bone and external cortical bone correlated with Z score (r = -0.975, p = 0.005 and r = -0.880, p = 0.021 respectively). We found no significant correlations between cortical thickness or porosity and DXA parameters for either external cortical bone or internal cortical bone. Our results suggest that a greater degree of kidney disease is associated with thinner cortices, eventually contributing to the higher fracture rate observed in the chronic kidney disease population. In predialysis patients, parathyroid hormone seems to have a modulating effect on both trabecular bone and cortical bone, particularly in external cortical bone.

Kidney Graft Leiomyosarcoma: A Case Report.

BACKGROUND: Kidney transplant (KT) recipients have a higher incidence of malignancy than the general population. Smooth muscle tumors (SMT), including leiomyosarcoma, are rare in kidney transplant recipients, and most cases are associated with Epstein-Barr virus (EBV) infection. CASE REPORT: A 57-year-old man received a deceased donor kidney transplant at the age of 53 years, with 5 human leukocyte antigen (HLA) mismatches. Before the transplantation, the patient was IgG positive for EBV viral capsid antigen (VCA), negative for IgM EBV VCA, and also negative for IgG EBV nuclear antigen (EBNA), suggesting a prior EBV infection. He received immunosuppressive induction with basiliximab, and maintenance with tacrolimus, mycophenolate mofetil, and prednisolone. Two years after transplantation, he had an acute cellular rejection episode treated with methylprednisolone. An increased graft size was found 4 years after transplantation. A computed tomographic scan showed 3 solid tumors involving the renal graft with extension to the perinephric fat; no secondary localizations were found. A nephrectomy of the graft was performed. The histologic diagnosis was a high-grade leiomyosarcoma. In situ hybridization for EBV was negative. Nine months after nephrectomy, local recurrence was diagnosed. The surgical approach was unsuccessful, and the patient died after a brief period. CONCLUSION: Kidney leiomyosarcoma is a very rare clinical condition. Most of these neoplasms that arise in transplanted recipients are associated with EBV in tumor tissue. Only one case of renal graft leiomyosarcoma without EBV RNA in the tumor has been previously reported.

JC polyomavirus nephropathy confirmed by using an in-house polymerase chain reaction method.

We report the case of an isolated JC virus (JCV) infection, without co-infection by polyoma BK virus (BKV), associated with nephropathy 4 years after kidney transplantation. Clinical suspicion followed the observation of a decrease in estimated glomerular filtration rate (eGFR) and a renal allograft biopsy revealing polyomavirus-associated tubulointerstitial nephritis and positivity for SV40. An in-house real-time polymerase chain reaction assay, targeting the presence of JCV and the absence of BKV in biopsy tissue, confirmed diagnosis. Thirteen months after diagnosis, and following therapeutic measures, eGFR remains stable.

Femoral bone mineral density reflects histologically determined cortical bone volume in hemodialysis patients.

UNLABELLED: We evaluated the associations between dual energy X-ray absorptiometry (DXA) and histologically determined cancellous and cortical bone volume by controlling for vascular calcifications and demographic variables in hemodialysis (HD) patients. Femoral bone mineral density (f-BMD) was associated with cortical porosity. INTRODUCTION: Assessment of bone mass in chronic kidney disease patients is of clinical importance because of the association between low bone volume, fractures, and vascular calcifications. DXA is used for noninvasive assessment of bone mass whereby vertebral results reflect mainly cancellous bone and femoral results reflect mainly cortical bone. Bone histology allows direct measurements of cancellous and cortical bone volume. The present study evaluates the association between DXA and histologically determined cancellous and cortical bone volumes in HD patients. METHODS: In 38 HD patients, DXA was performed for assessment of bone mass, anterior iliac crest bone biopsies for bone volume, and multislice computed tomography for vascular calcifications. RESULTS: While lumbar bone mineral density (l-BMD) by DXA was not associated with histologically measured cancellous bone volume, coronary Agatson score showed a borderline statistically significant association (P = 0.055). When controlled for age and dialysis duration, f-BMD by DXA was associated with cortical porosity determined by histology (P = 0.005). CONCLUSIONS: The usefulness of l-BMD for predicting bone volume is limited most probably because of interference by soft tissue calcifications. In contrast, f-BMD shows significant association with cortical porosity.

Human herpes virus-8 serology and DNA analysis in recipients of renal allografts showing Kaposi's sarcoma and their respective donors.

Kaposi's sarcoma (KS) developed among 11 of 416 renal allograft recipients transplanted between 1985 and 2000. Only 3 among 364 Caucasian recipients developed KS, while it affected 8 of 52 Black patients, all of whom had been born in African countries (P <.001). All patients had their immunosuppression reduced; two also received daunorubicin and one received electrotherapy. Three patients developed accelerated renal allograft dysfunction, probably due to the reduced immunosuppression. Remission of KS was observed in seven patients, while lesions stabilized or improved partially in the other four. After resuming dialysis 2 of 11 patients died; both were in KS remission. Human herpes virus-8 (HHV-8) serology and DNA analysis was evaluated in sera obtained from seven donors: all were negative. Conversely, among eight sera collected pretransplant from the nine living recipients, HHV-8 IgG was detected in six and DNA was present in one. HHV-8 IgG was expressed in all patients (9/9) at some point posttransplant; DNA was detected in three patients. Therefore, the robust ethnic predisposition to KS was associated with a high pretransplant prevalence of HHV-8 among African recipients. Although some seroconversions were detected posttransplant, there was no evidence for donor-to-recipient transmission.

[Consequences of the correction of post-transplantation hypophosphatemia on mineral metabolism]. / Consequências no metabolismo mineral da correcção da hipofosfatemia pós-transplante.

AIM: To study the effect of the correction of post-transplantation Hypophosphatemia on mineral metabolism. PATIENTS: 15 patients with renal transplants for 3 to 12 months, Serum Creatinine "177 micmol/1, were treated with oral phosphorus (P) for persistent hypophosphatemia. METHODS: 3 periods of blood and urine collection at intervals of 3 weeks. T1 under basal treatment with oral P, T2 after 3 weeks off medication with P, Ca, or P binders. T3 3 weeks after going back on oral P supplements. RESULTS: Serum P dropped from T1 to T2 (1.03 +/- 0.03 mmol/L to 0.83 +/- 0.03 mmol/L, p "0.0001), rising again in T3 to 1.06 +/- 0.03 mmol/L. From T1 to T2, PTHi decreased from 95.4 +/- 8.7 to 66.8 8.9pg/ml), osteocalcin rose from 3.8 +/- 1.2 to 16.6 +/- 2.3ng/ml (p<0.001) and 25-Vit D rose from 16.7 +/- 1.9 to 21.4 +/- 2.1 ng/l (p<0.001), with the reversal of these changes from T2 to T3 when serum P increased once again. There was a significant correlation between serum P and PTHi and serum P and 25-Vit D. There were no significant variations of the serum Ca, Alk. Phosph., ICTP and CaFE values in the three periods. CONCLUSIONS: 1-Serum P never dropped below 0.55 mmol/L, which had no clinical consequences, 2- When the P dropped, PTHi also dropped and osteocalcin and 25-Vit D rose, without any major variation in bone catabolism, 3- Correction of hypophosphatemia may delay recovery from secondary hyperparathyroidism.

[Value of percutaneous nephrostomy in nephrology]. / Interesse da nefrostomia percutânea em nefrologia.

Percutaneous Nephrostomy (P.N.) has been traditionally used by Urologists. The authors seek to demonstrate the interest of its mastering by members of Nephrology teams, by reviewing 27 cases of unilateral or bilateral P.N. performed in a Nephrology unit from 1983 to 1991. The single most frequent indication for P.N. was Acute or Chronic Renal Insufficiency of obstructive etiology (21 cases), followed by infected Hydronephrosis (4), assessment of residual function of an obstructed Kidney (1) and renal colic in a pregnant woman (1). There were no major complications of the procedure. P.N. allowed correction of metabolic derangements and of infections, enabling the definitive etiologic solution to take place in a clearly favourable clinical context.

[Assessment of iron requirements during treatment of anemia with recombinant human erythropoietin in patients with chronic renal insufficiency under hemodialysis]. / Avaliação das necessidades em ferro durante o tratamento da anemia com eritropoietina humana recombinante nos doentes com insuficiência renal crónica em hemodiálise.

Iron deficiency occurs often in patients with recombinant human Erythropoietin (rhEPO) therapy in chronic renal failure (CRF) associated anemia. We have studied 10 patients with CRF on regular hemodialysis (HD), female = 8, male = 2, average age = 49 [32 to 72], time on HD 44.2 +/- 25.0 months. Before starting rhEPO, the mean hemoglobin value was 7.36 +/- 1.29 gr/dl, the mean ferritin 695.4 +/- 276.0 ng/ml, the mean serum iron 160.3 +/- 49.5 micrograms/dl and the mean transferrin saturation 55.3 +/- 12.6%. Transfusional requirements in the 12 months Pré-rhEPO were 10.9 +/- 3.2 units. The rhEPO dose level was 80 U/kg body weight (3 times a week, after HD) in the Correction Period (mean time = 46.7 +/- 18.6 days), being reduced afterwards in order to remain target Hb stable between 10 and 11 gr/dl. Iron deficiency was detected (transferrin iron saturation less than 16% or serum ferritin less than 30 ng/ml) in 5 of the 10 patients. Patients have been divided into two Groups (GI--patients which developed iron deficiency; GII--patients which remained iron replete). There were no significant differences between GI and GII in the serum iron, transferrin and transferrin saturation values of the Pré-rhEPO. Serum ferritin in the Pré-rhEPO was lower in GI than GII (GI = 489.2 +/- 23.6 ng/ml; GII = 901.6 +/- 96.4 ng/ml; p less than 0.01). Falls in the transferrin iron saturation during the Correction Period and 3, 6 and 12 months and in the serum ferritin at 3, 6 and 12 months versus Pré-rhEPO have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)