Diagnostic Usefulness of the Protein Energy Wasting Score in Prevalent Hemodialysis Patients.

OBJECTIVE: To study whether the score proposed by the International Society of Renal Nutrition and Metabolism to define the protein energy wasting (PEW) syndrome has diagnostic validity in patients undergoing dialysis. DESIGN AND METHODS: Cross-sectional study including 468 prevalent hemodialysis patients from Canary Islands, Spain. Individual PEW syndrome criteria and the number of PEW syndrome categories were related to other objective markers of PEW using linear and logistic regression analyses: subjective global assessment, handgrip strength, bioimpedance-assessed body composition, and levels of high-sensitivity C-reactive protein. RESULTS: Study participants (34% women) had a median age of 66 years, 37 months of maintenance dialysis, and 50% were diabetics. About 23% of patients had PEW (≥3 PEW categories), and 68% were at risk of PEW (1-2 PEW categories). Low prealbumin was the most frequently found derangement (52% of cases), followed by low albumin (46%), and low protein intake (35%). Across higher number of PEW syndrome categories, patients showed a longer dialysis vintage and had lower creatinine, triglycerides, and transferrin (P for trend <.001 for all). All nutritional assessments not included in the PEW definition worsened across higher number of PEW categories. In multivariable regression analyses, there was a linear inverse relationship between muscle and fat mass as well as handgrip strength with the number of PEW syndrome categories. Likewise, the proportion of subjective global assessment-defined malnutrition and serum concentration of C-reactive protein gradually increased despite adjustment for confounders (P for trend <.05 for all). CONCLUSION: The PEW score reflects systemic inflammation, malnutrition and wasting among dialysis patients and may thus be used for diagnostic purposes.

Osteoporosis management in patients with chronic kidney disease (ERCOS Study): A challenge in nephrological care.

Fracture risk assessment in patients with chronic kidney disease (CKD) has been included in the CKD-MBD ("Chronic Kidney Disease-Mineral and Bone Disorders") complex in international and national nephrology guidelines, suggesting for the first time the assessment of bone mineral density (BMD) if the results can influence therapeutic decision-making. However, there is very little information on actual clinical practice in this population. The main objective of the ERCOS (ERC-Osteoporosis) study is to describe the profile of patients with CKD G3-5D with osteoporosis (OP) and/or fragility fractures treated in specialized nephrology, rheumatology and internal medicine clinics in Spain. Fifteen centers participated and 162 patients (mostly women [71.2%] postmenopausal [98.3%]) with a median age of 77 years were included. Mean estimated glomerular filtration rate (eGFR) was 36 mL/min/1.73 m2 and 38% of the included patients were on dialysis. We highlight the high frequency of prevalent fragility fractures [37.7%), mainly vertebral (52.5%) and hip (24.6%)], the disproportionate history of patients with glomerular disease compared to purely nephrological series (corticosteroids) and undertreatment for fracture prevention, especially in nephrology consultations. This study is an immediate call to action with the dissemination of the new, more proactive, clinical guidelines, and underlines the need to standardize a coordinated and multidisciplinary care/therapeutic approach to these patients in an efficient way to avoid current discrepancies and therapeutic nihilism.

Real-world management of hyperphosphataemia with sucroferric oxyhydroxide: the VELREAL multicentre study.

BACKGROUND: The efficacy and safety of sucroferric oxyhydroxide (SO) have been reported in clinical trials. However, real-life data are scarce. This study presents data on the use, efficacy and safety of SO in real clinical practice. METHODS: We performed a retrospective multicentre study, without any influence on the prescription decisions, that included 220 patients from 11 Spanish centres. Demographic, treatment, analytical and nutritional parameters and adherence, side effects and dropout rates were collected during 6 months. RESULTS: SO was initiated due to inadequate control of serum phosphate (P) in 70% of participants and in 24.5% to reduce the number of tablets. Monotherapy with SO increased from 44% to 74.1%, with a reduction in the average daily number of sachets/tablets from six to two. Serum P decreased by 20% (4.6 ± 1.2 versus 5.8 ± 1.3 mg/dL; P < 0.001), with a significant reduction in intact parathyroid hormone levels (P < 0.01). The percentage of patients with adequate serum P control at threshold levels of 5 and 4.5 mg/dL increased by 45.4% and 35.9%, respectively. Serum ferritin was not modified, while the transferrin saturation index increased significantly (P = 0.04). Serum albumin and normalized protein catabolic rate, when normalized by serum P, increased, averaging 37% and 39%, respectively (P < 0.001). Adherent patients increased from 28.2% to 52.7%. Adverse effects were reported by 14.1% of participants, with abandonment of treatment in 9.5%. CONCLUSIONS: The use of SO in real-life results in better control of serum P, a reduction in the number of tablets and an improvement in therapeutic adherence. In addition, it may be beneficial with regards to secondary hyperparathyroidism and nutritional status.

Anti-inflammatory profile of paricalcitol in kidney transplant recipients. / Perfil antiinflamatorio del paricalcitol en el receptor de trasplante renal.

BACKGROUND AND OBJECTIVES: Paricalcitol, a selective vitamin D receptor activator, is used to treat secondary hyperparathyroidism in kidney transplant patients. Experimental and clinical studies in non-transplant kidney disease patients have found this molecule to have anti-inflammatory properties. In this exploratory study, we evaluated the anti-inflammatory profile of paricalcitol in kidney-transplant recipients. METHODS: Thirty one kidney transplant recipients with secondary hyperparathyroidism completed 3 months of treatment with oral paricalcitol (1µg/day). Serum concentrations and gene expression levels of inflammatory cytokines in peripheral blood mononuclear cells were analysed at the beginning and end of the study. RESULTS: Paricalcitol significantly decreased parathyroid hormone levels with no changes in calcium and phosphorous. It also reduced serum concentrations of interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) by 29% (P<0.05) and 9.5% (P<0.05) compared to baseline, respectively. Furthermore, gene expression levels of IL-6 and TNF-α in peripheral blood mononuclear cells decreased by 14.1% (P<0.001) and 34.1% (P<0.001), respectively. The ratios between pro-inflammatory cytokines (TNF-α and IL-6) and anti-inflammatory cytokines (IL-10), both regarding serum concentrations and gene expression, also experienced a significant reduction. CONCLUSIONS: Paricalcitol administration to kidney transplant recipients has been found to have beneficial effects on inflammation, which may be associated with potential clinical benefits.

Anaemia and fever in Kidney transplant. The role of human parvovirus B19. / Anemia y fiebre en el postrasplante renal: su relación con el parvovirus humano B19.

Infections remain an issue of particular relevance in renal transplant patients, particularly viral infections. Human parvovirus B19 infection causes severe refractory anaemia, pancytopenia and thrombotic microangiopathy. Its presence is recognized by analysing blood polymerase chain reaction (PCR) and by the discovery of typical giant proerythroblasts in the bone marrow. We report the case of a 65 year-old man with a history of deceased donor renal transplant in September 2014. At 38 days after the transplant, the patient presented progressive anaemia that was resistant to erythropoiesis-stimulating agents. At 64 days after transplant, hyperthermia occurred with progressive deterioration of the patient's general condition. The viral serology and the first blood PCR for human parvovirus B19 were both negative. At 4 months and 19 days after, a bone marrow biopsy was conducted, showing giant erythroblasts with nuclear viral inclusions that were compatible with parvovirus; a PCR in the tissue confirmed the diagnosis. A second blood PCR was positive for parvovirus. After treatment with intravenous immunoglobulin and the temporary discontinuation of mycophenolate mofetil, a complete remission of the disease occurred, although the blood PCR for parvovirus B19 remained positive, so monitoring is necessary for future likely recurrence.

Effect of Paricalcitol on FGF-23 and Klotho in Kidney Transplant Recipients.

BACKGROUND: Paricalcitol decreases intact parathyroid hormone and the frequency of secondary hyperparathyroidism after kidney transplantation. This proof-of-concept study aimed to assess the effect of paricalcitol on fibroblast growth factor-23/KLOTHO axis in renal transplants. METHODS: Twenty-nine subjects with secondary hyperparathyroidism received oral paricalcitol 1 µg/d for 3 months, and 8 patients matched by age, sex, and creatinine clearance, but with intact parathyroid hormone less than 100 pg/mL, were included as controls. RESULTS: Intact parathyroid hormone decreased in paricalcitol-treated patients (P < 0.0001). Serum fibroblast growth factor-23 enhanced (P < 0.01), whereas KLOTHO concentrations showed a trend to increase (P = 0.067). KLOTHO gene expression in peripheral blood mononuclear cells increased by 45.7% in paricalcitol-treated patients (P < 0.01), without change in controls. Paricalcitol administration resulted in a median percent decrease of 56% in methylated DNA levels of KLOTHO promoter (P < 0.001). The ratio of the unmethylated/methylated KLOTHO promoter DNA did not change in controls, but it increased by 177% in paricalcitol-treated subjects (P < 0.0001). The increase in this ratio was independently associated with the change in serum KLOTHO (r = 0.55, P < 0.01) and messenger RNA expression levels (r = 0.40, P < 0.05). CONCLUSIONS: Paricalcitol administration to renal transplant patients significantly reduced intact parathyroid hormone and increased fibroblast growth factor-23, with a trend to increase in serum KLOTHO. Paricalcitol-treated patients showed a decrease in the methylation of the KLOTHO promoter with an increment in the ratio of un-methyated/methylated DNA, which was associated with an increase of KLOTHO gene expression levels and serum KLOTHO concentrations. Long-term studies are needed to assess whether paricalcitol-induced increase in KLOTHO gene expression and serum concentrations may translate into beneficial clinical effects.

Renal Replacement Therapy: Purifying Efficiency of Automated Peritoneal Dialysis in Diabetic versus Non-Diabetic Patients.

BACKGROUND: In order to reduce the cardiovascular risk, morbidity and mortality of peritoneal dialysis (PD), a minimal level of small-solute clearances as well as a sodium and water balance are needed. The peritoneal dialysis solutions used in combination have reduced the complications and allow for a long-time function of the peritoneal membrane, and the preservation of residual renal function (RRF) in patients on peritoneal dialysis (PD) is crucial for the maintenance of life quality and long-term survival. This retrospective cohort study reviews our experience in automatic peritoneal dialysis (APD) patients, with end-stage renal disease (ESRD) secondary to diabetic nephropathy (DN) in comparison to non-diabetic nephropathy (NDN), using different PD solutions in combination. DESIGN: Fifty-two patients, 29 diabetic and 23 non-diabetic, were included. The follow-up period was 24 months, thus serving as their own control. RESULTS: The fraction of renal urea clearance (Kt) relative to distribution volume (V) (or total body water) (Kt/V), or creatinine clearance relative to the total Kt/V or creatinine clearance (CrCl) decreases according to loss of RRF. The loss of the slope of RRF is more pronounced in DN than in NDN patients, especially at baseline time interval to 12 months (loss of 0.29 mL/month vs. 0.13 mL/month, respectively), and is attenuated in the range from 12 to 24 months (loss of 0.13 mL/month vs. 0.09 mL/month, respectively). Diabetic patients also experienced a greater decrease in urine output compared to non-diabetic, starting from a higher baseline urine output. The net water balance was adequate in both groups during the follow up period. Regarding the balance sodium, no inter-group differences in sodium excretion over follow up period was observed. In addition, the removal of sodium in the urine output decreases with loss of renal function. The average concentration of glucose increase in the cycler in both groups (DN: baseline 1.44 ± 0.22, 12 months 1.63 ± 0.39, 24 months 1.73 ± 0.47; NDN: baseline 1.59 ± 0.40, 12 months 1.76 ± 0.47, 24 months 1.80 ± 0.46), in order to maintain the net water balance. The daytime dwell contribution, the fraction of day and the renal fraction of studies parameters provide sustained benefit in the follow-up time, above 30%. CONCLUSIONS: The wet day and residual renal function are determinants in the achievement of the objective dose of dialysis, as well as in the water and sodium balance. The cause of chronic kidney disease (CKD) does not seem to influence the cleansing effectiveness of the technique.

Water overload as a biomarker for heart failure and acute renal failure.

Heart failure (HF) and acute renal failure (ARF) are two very prevalent entities in our environment which impact directly and synergistically in the morbidity and mortality of our patients. ARF, when oligoanuric, often leads to water overload. It represents the precipitating core of the mechanism of acute decompensation of the HF and is associated with the worsening of symptoms, hospitalisation and death. Determining the water balance in HF can be complex and depends, largely, on the underlying pathophysiology. New biomarkers and new technologies are proving to be useful for the detection and identification of risk of acutely decompensated HF that may allow early intervention and reversal of the ARF that translates into better clinical outcomes.

The occurrence or fibrillary glomerulonephritis in patients with diabetes mellitus may not be coincidental: a report of four cases.

Although clinical presentation of fibrillary glomerulonephritis is similar to most forms of glomerulonephritis, it is usually difficult to make the diagnosis. Clinical manifestations include proteinuria, microscopic haematuria, nephrotic syndrome, and impairment of renal function. A diagnosis of fibrillary glomerulonephritis is only confirmed by renal biopsy and it must comprise electronmicroscopy-verified ultrastructural findings. We report four cases between 45-50 years old with documented type 2 diabetes mellitus (T2DM) and arterial hypertension. All patients were found to have fibrils on kidney biopsy. The differential diagnosis of fibrils in the setting of diabetes mellitus is also discussed.

Transplantectomy following renal graft failure.

Approximately 4%-10% of incident patients on dialysis have a non-functioning kidney graft, and according to series, as many as 32% require transplantectomy for a variety of reasons. Mortality in these patients is significantly higher than in those with a functioning graft or on renal replacement therapy without having received a graft. Graft intolerance syndrome, early graft loss, severe proteinuria, recurring pyelonephritis or neoplasia, and chronic inflammation syndrome have all been proposed as indications for transplantectomy. Chronic inflammation syndrome occurs in patients with high levels of inflammatory markers (C-reactive protein), anaemia resistant to treatment with erythropoiesis stimulators, and malnutrition markers. This inflammatory state is provoked by the graft, and reverts when a transplantectomy is performed, as several studies have shown. We have reviewed the medical literature published on this topic, the indications for transplantectomy and embolectomy, their advantages and disadvantages, the incidence of graft intolerance syndrome, and the pathophysiology of chronic inflammation syndrome, as well as the currently proposed therapeutic management algorithm.