Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000 mg/day and not exceeding 1500 mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Safety and immediate humoral response of COVID-19 vaccines in chronic kidney disease patients: the SENCOVAC study.

BACKGROUND: Chronic kidney disease (CKD) patients are at high-risk for severe coronavirus disease 2019 (COVID-19). The multicentric, observational and prospective SENCOVAC study aims to describe the humoral response and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in CKD patients. Safety and immediate humoral response results are reported here. METHODS: Four cohorts of patients were included: kidney transplant (KT) recipients, and haemodialysis (HD), peritoneal dialysis (PD) and non-dialysis CKD patients from 50 Spanish centres. Adverse events after vaccine doses were recorded. At baseline and on Day 28 after the last vaccine dose, anti-Spike antibodies were measured and compared between cohorts. Factors associated with development of anti-Spike antibodies were analysed. RESULTS: A total of 1746 participants were recruited: 1116 HD, 171 PD, 176 non-dialysis CKD patients and 283 KT recipients. Most patients (98%) received mRNA vaccines. At least one vaccine reaction developed after the first dose in 763 (53.5%) and after the second dose in 741 (54.5%) of patients. Anti-Spike antibodies were measured in the first 301 patients. At 28 days, 95% of patients had developed antibodies: 79% of KT, 98% of HD, 99% of PD and 100% of non-dialysis CKD patients (P < 0.001). In a multivariate adjusted analysis, absence of an antibody response was independently associated with KT (odds ratio 20.56, P = 0.001) and with BNT162b2 vaccine (odds ratio 6.03, P = 0.023). CONCLUSION: The rate of anti-Spike antibody development after vaccination in KT patients was low but in other CKD patients it approached 100%, suggesting that KT patients require persistent isolation measures and booster doses of a COVID-19 vaccine. Potential differences between COVID-19 vaccines should be explored in prospective controlled studies.

Criteria for classification of protein-energy wasting in dialysis patients: impact on prevalence.

Malnutrition is highly prevalent in dialysis patients and associated with poor outcomes. In 2008, protein-energy wasting (PEW) was coined by the International Society of Renal Nutrition and Metabolism (ISRNM), as a single pathological condition in which undernourishment and hypercatabolism converge. In 2014, a new simplified score was described using serum creatinine adjusted for body surface area (sCr/BSA) to replace a reduction of muscle mass over time in the muscle wasting category. We have now compared PEW-ISRNM 2008 and PEW-score 2014 to evaluate the prevalence of PEW and the risk of death in 109 haemodialysis patients. This was a retrospective analysis of cross sectional data with a median prospective follow-up of 20 months. The prevalence of PEW was 41 % for PEW-ISRNM 2008 and 63 % for PEW-score 2014 (P <0·002). Using PEW-score 2014: twenty-nine patients (27 %) had severe malnutrition (PEW-score 2014 0-1) and forty (37 %) with moderate malnutrition (score 2). Additionally, thirty-three (30 %) patients had mild wasting and only seven patients (6 %) presented a normal nutritional status. sCr/BSA correlated with lean total mass (R 0·46. P<0·001). A diagnosis of PEW according to PEW-score 2014, but not according to PEW-ISRNM 2008, was significantly associated with short-term mortality (P=0·0349) in univariate but not in multivariate analysis (P=0·069). In conclusion, the new PEW-score 2014 incorporating sCr/BSA identifies a higher number of dialysis PEW patients than PEW-ISRNM 2008. Whereas PEW-score-2014 provides timelier and therefore more clinically relevant information, its association with early mortality needs to be confirmed in larger studies.

Reactions to Synthetic Membranes Dialyzers: Is there an Increase in Incidence?

BACKGROUND: Reactions to dialyzers used in dialysis have been reported more frequently in recent years. Evidence, however, shows that the reaction rate has remained stable for years. SUMMARY: One explanation for the apparent increase in publication frequency could be the lack of knowledge that dialyzer reactions may well occur with biocompatible membranes. Studies showed that the cause of these reactions is very diverse and varied, involving multiple materials. However, polyvinylpyrrolidone continues to be the main suspect, but without conclusive results. There are no differences between the different fibers, and although polysulfone is the most described, it is also the most used. Key Messages: The change to cellulose triacetate continues to be the most appropriate form of treatment. The classification of these reactions into type A and B complicates the diagnosis, and its true usefulness is in doubt.

Eculizumab in secondary atypical haemolytic uraemic syndrome.

Background: Complement dysregulation occurs in thrombotic microangiopathies (TMAs) other than primary atypical haemolytic uraemic syndrome (aHUS). A few of these patients have been reported previously to be successfully treated with eculizumab. Methods: We identified 29 patients with so-called secondary aHUS who had received eculizumab at 11 Spanish nephrology centres. Primary outcome was TMA resolution, defined by a normalization of platelet count (>150 × 10 9 /L) and haemoglobin, disappearance of all the markers of microangiopathic haemolytic anaemia (MAHA), and improvement of renal function, with a ≥25% reduction of serum creatinine from the onset of eculizumab administration. Results: Twenty-nine patients with secondary aHUS (15 drug-induced, 8 associated with systemic diseases, 2 with postpartum, 2 with cancer-related, 1 associated with acute humoral rejection and 1 with intestinal lymphangiectasia) were included in this study. The reason to initiate eculizumab treatment was worsening of renal function and persistence of TMA despite treatment of the TMA cause and plasmapheresis. All patients showed severe MAHA and renal function impairment (14 requiring dialysis) prior to eculizumab treatment and 11 presented severe extrarenal manifestations. A rapid resolution of the TMA was observed in 20 patients (68%), 15 of them showing a ≥50% serum creatinine reduction at the last follow-up. Comprehensive genetic and molecular studies in 22 patients identified complement pathogenic variants in only 2 patients. With these two exceptions, eculizumab was discontinued, after a median of 8 weeks of treatment, without the occurrence of aHUS relapses. Conclusion: Short treatment with eculizumab can result in a rapid improvement of patients with secondary aHUS in whom TMA has persisted and renal function worsened despite treatment of the TMA-inducing condition.

Cortisol levels are associated with mortality risk in hemodialysis patients.

BACKGROUND: End-stage renal disease (ESRD) conveys high mortality risk by complex mechanisms not fully elucidated but possibly linked to hormonal abnormalities, including cortisol. Whereas a high serum cortisol level has recently been linked with increased mortality in the general population, there is scarce information on the clinical associates and prognostic value of cortisol levels in ESRD. PATIENTS AND METHODS: Prospective study of prevalent hemodialysis patients (n = 75), mostly non-diabetic (76%), where cortisol levels were assessed and patients were afterwards followed for a median of 20 (interquartile range (IQR) 8 - 31) months. RESULTS: Cortisol levels were negatively correlated with plasma sodium (Rho = -0.26. p < 0.025) and positively correlated with C-reactive protein (CRP; Rho = 0.26, p = 0.027). The association with CRP remained independent of multiple confounders. Baseline cortisol levels of those who died were higher than of those who survived (19.8 ± 6.9 vs. 15.3 ± 5.7 mcg/dL, p = 0.0083). Kaplan-Meier analysis showed that patients with cortisol levels within the highest tertile (≥ 18 mcg/dL) were at increased risk of death. Cortisol was associated with risk of death both in crude and adjusted Cox proportional hazards models (HR 1.09 (1.021 - 1.167) p = 0.011; and 1.16 (1.027 - 1.309), p = 0.01, respectively)). CONCLUSIONS: High serum concentrations of cortisol were associated with a state of inflammation and independently identified a subgroup of chronic hemodialysis patients at a high mortality risk.

Definition and evolution of the concept of sarcopenia.

Sarcopenia and dynapenia are two terms associated with ageing that respectively define the loss of muscle mass and strength. In 2018, the European Working Group on Sarcopenia in Older People (EWGSOP) introduced the EWGSOP2 diagnostic algorithm for sarcopenia, which integrates both concepts. It consists of 4 sequential steps: screening for sarcopenia, examination of muscle strength, assessment of muscle mass and physical performance; depending on these last 3 aspects sarcopenia is categorised as probable, confirmed, and severe respectively. In the absence of validation of the EWGSOP2 algorithm in various clinical contexts, its use in haemodialysis poses several limitations: (a) low sensitivity of the screening, (b) the techniques that assess muscle mass are not very accessible, reliable, or safe in routine clinical care, (c) the sequential use of the magnitudes that assess dynapenia and muscle mass do not seem to adequately reflect the muscular pathology of the elderly person on dialysis. We reflect on the definition of sarcopenia and the use of more precise terms such as "myopenia" (replacing the classic concept of sarcopenia to designate loss of muscle mass), dynapenia and kratopenia. Prospective evaluation of EWGSOP2 and its comparison with alternatives (i.e. assessment of kratopenia and dynapenia only; steps 2 and 4) is proposed in terms of its applicability in clinical routine, resource consumption, identification of at-risk individuals and impact on events.

Displacing the Burden: A Review of Protein-Bound Uremic Toxin Clearance Strategies in Chronic Kidney Disease.

Uremic toxins (UTs), particularly protein-bound uremic toxins (PBUTs), accumulate in chronic kidney disease (CKD) patients, causing significant health complications like uremic syndrome, cardiovascular disease, and immune dysfunction. The binding of PBUTs to plasma proteins such as albumin presents a formidable challenge for clearance, as conventional dialysis is often insufficient. With advancements in the classification and understanding of UTs, spearheaded by the European Uremic Toxins (EUTox) working group, over 120 molecules have been identified, prompting the development of alternative therapeutic strategies. Innovations such as online hemodiafiltration aim to enhance the removal process, while novel adsorptive therapies offer a means to address the high affinity of PBUTs to plasma proteins. Furthermore, the exploration of molecular displacers, designed to increase the free fraction of PBUTs, represents a cutting-edge approach to facilitate their dialytic clearance. Despite these advancements, the clinical application of displacers requires more research to confirm their efficacy and safety. The pursuit of such innovative treatments is crucial for improving the management of uremic toxicity and the overall prognosis of CKD patients, emphasizing the need for ongoing research and clinical trials.

Subclinical versus overt obesity in dialysis patients: more than meets the eye.

BACKGROUND: Obesity is an important problem in the epidemic of chronic kidney disease (CKD). Obesity is usually diagnosed by body mass index (BMI), but this metric has limitations as a measure of adiposity in CKD patients. Simple anthropometric tools, like skinfold thickness measurements, have been shown to be a better test to classify obesity among those with CKD. METHODS: The prevalence of obesity was estimated by BMI (>30 kg/m(2)) and by skinfold thickness-estimated body fat (>25% in men and 35% in women) in two cohorts comprising 284 incident dialysis and 209 prevalent haemodialysis (HD) patients from Sweden. Patient characteristics were compared among individuals with differing diagnosis. RESULTS: BMI obesity cut-offs misdiagnosed many patients (>50%) with excess adiposity. Obesity, estimated by BMI, was present in 9 and 10% of incident and prevalent dialysis patients, respectively. When estimated by percentage of body fat, the prevalence of obesity rose to 64 and 65%. In both cohorts, a large proportion of patients (55%) were obese in the context of a normal BMI (termed as subclinical obesity). These individuals were older, presented more co-morbidity and lower surrogates of muscle mass [handgrip strength, arm muscle circumference or insulin-growth factor (IGF)-1 levels] than those diagnosed by both methods (termed overt obesity). CONCLUSION: A BMI of <30 kg/m(2) does not exclude the presence of excess adiposity. Subclinical obesity is a frequent condition in dialysis patients, and the clinical consequences of this finding deserve further consideration.

Correction of hypocalcemia allows optimal recruitment of FGF-23-dependent phosphaturic mechanisms in acute hyperphosphatemia post-phosphate enema.

Both parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) are phosphaturic hormones. These hormones should increase in response to phosphate excess. However, they also regulate serum calcium; PTH increases serum calcium concentration and FGF23 suppresses renal production of calcitriol, favoring hypocalcemia. We report the case of an 83-year-old woman with hyperphosphatemia and hypocalcemia resulting from phosphate-containing enemas. PTH and calcitriol increased in response to hypocalcemia, and FGF23 increased in response to hyperphosphatemia. Unexpectedly, peak FGF23 did not coincide with peak serum phosphate. Rather, peak FG23 was observed only after severe hypocalcemia was partially corrected with exogenous calcium administration, even though serum phosphate had been already decreasing for 32 h. Correction of severe hypocalcemia was thus associated with peak FGF23 values and with a precipitous decrease in PTH. Peak FGF23 was followed by an accelerated decrease in serum phosphate and significant phosphaturia. This clinical report is consistent with experimental data in rats showing a blunted FGF23 response to high phosphate in the presence of severe hypocalcemia. Thus, complementary experimental and clinical data suggest that partial correction of severe hypocalcemia is required for optimal FGF23-mediated phosphaturia, which takes place despite correction of PTH levels. We believe this the first human report suggesting blunting of the FGF23 response to high phosphate by severe hypocalcemia.

Sarcopenia and Mortality in Older Hemodialysis Patients.

(1) Sarcopenia is a progressive loss of skeletal muscle mass and strength. The aim of this study was to determine the association of sarcopenia, defined according to the Working Group on Sarcopenia in Older People (EWGSOP2) diagnostic criteria, with mortality at 24 months in very elderly hemodialysis patients. (2) A prospective study was conducted in 60 patients on chronic hemodialysis who were older than 75 years. Sarcopenia was diagnosed according to EWGSOP2 criteria. Additionally, clinical, anthropometric and analytical variables and body composition by bioimpedance were assessed. The date and cause of death were recorded during 2 years of follow-up. (3) Among study participants, 41 (68%) were men, the mean age 81.85 ± 5.58 years and the dialysis vintage was 49.88 ± 40.29 months. The prevalence of probable sarcopenia was 75% to 97%, depending on the criteria employed: confirmed sarcopenia ranged from 37 to 40%, and severe sarcopenia ranged from 18 to 37%. A total of 30 (50%) patients died over 24 months. Sarcopenia probability variables were not related to mortality. In contrast, sarcopenia confirmation (appendicular skeletal muscle mass, ASM) and severity (gait speed, GS) variables were associated with mortality. In multivariate analysis, the hazard ratio (95% confidence interval) for all-cause death was 3.03 (1.14-8.08, p = 0.028) for patients fulfilling ASM sarcopenia criteria and 3.29 (1.04-10.39, p = 0.042) for patients fulfilling GS sarcopenia criteria. (4) The diagnosis of sarcopenia by EWGSOP2 criteria is associated with an increased risk of all-cause death in elderly dialysis patients. Specifically, ASM and GS criteria could be used as mortality risk markers in elderly hemodialysis patients. Future studies should address whether the early diagnosis and treatment of sarcopenia improve outcomes.

Evaluation of the impact of an intradialytic exercise programme on sarcopaenia in very elderly haemodialysis patients.

Sarcopaenia is a highly prevalent condition in persons on haemodialysis (HD). In stable very elderly (75-95 years old) persons on chronic HD, we prospectively studied the European Working Group on Sarcopaenia in Older People (EWGSOP2) steps stability over time in 37 controls and their response to a 12-week intradialytic lower limb exercise programme in 23 persons. Overall dropout was 15% and the main cause for dropout was death (8%). Thus 33 controls and 18 exercise participants were evaluated at 12 weeks. In controls, comorbidity, nutrition, dependency and frailty scales, anthropometric assessments, EWGSOP2 step values and the prevalence of suspected, confirmed and severe sarcopaenia as assessed by EWGSOP2 remained stable. In contrast, in persons who completed the exercise programme, a significant improvement in the five times sit-to-stand (STS-5) test was noted at the end of the 12-week exercise programme (19.2 ± 4.9-15.9 ± 5.9 seconds; P = .001), consistent with the lower limb nature of the exercise programme, that persisted 12 weeks after completion of the programme. Exercise also improved the Fried frailty scale (1.7 ± 1.0-1.1 ± 0.6; P = .004). In conclusion, EWGSOP2 steps remain stable in stable very elderly persons on HD and STS-5 is responsive to a short-term intradialytic lower limb exercise programme. These results may help define EWGSOP2-based primary endpoints in future large-scale clinical trials assessing exercise interventions.

Sarcopenia assessed by 4-step EWGSOP2 in elderly hemodialysis patients: Feasibility and limitations.

BACKGROUND: In 2019, EWGSOP2 proposed 4 steps to diagnose and assess sarcopenia. We aimed to quantify the prevalence of sarcopenia according to the EWGSOP2 diagnostic algorithm and to assess its applicability in elderly patients on hemodialysis. METHODS: Prospective study of 60 outpatients on chronic hemodialysis aged 75- to 95-years, sarcopenia was assessed according to the 4-step EWGSOP2: Find: Strength, Assistance walking, Rise from a chair, Climb stairs, and Falls (SARC-F); Assess: grip strength by dynamometry (GSD) and sit to stand to sit 5 (STS5); Confirm: appendicular skeletal muscle mass (ASM) by bioimpedance; Severity: gait speed (GS), Timed-Up and Go (TUG), and Short Physical Performance Battery (SPPB). RESULTS: The sequential four steps resulted in a prevalence of confirmed or severe sarcopenia of 20%. Most (97%) patients fulfilled at least one criterion for probable sarcopenia. The sensitivity of SARC-F for confirmed sarcopenia was low (46%). Skipping the SARC-F step increased the prevalence of confirmed and severe sarcopenia to 40% and 37%, respectively. However, 78% of all patients had evidence of dynapenia consistent with severe sarcopenia. Muscle mass (ASM) was normal in 60% of patients, while only 25% had normal muscle strength values (GSD). CONCLUSIONS: According to the 4-step EWGSOP2, the prevalence of confirmed or severe sarcopenia was low in elderly hemodialysis patients. The diagnosis of confirmed sarcopenia underestimated the prevalence of dynapenia consistent with severe sarcopenia. Future studies should address whether a 2-step EWGSOP2 assessment (Assess-Severity) is simpler to apply and may provide better prognostic information than 4-step EWGSOP2 in elderly persons on hemodialysis.

Ultrafiltration rate adjusted to body weight and mortality in hemodialysis patients.

BACKGROUND AND AIMS: Mortality among hemodialysis patients remains high. An elevated ultrafiltration rate adjusted by weight (UFR/W) has been associated with hypotension and higher risk of death and/or cardiovascular events. METHODS: We evaluated the association between UFR/W and mortality in 215 hemodialysis patients. The mean follow-up was 28 ±â€¯6.12 months. We collected patients' baseline characteristics and mean UFR/W throughout the follow-up. RESULTS: Mean UFR/W was 9.0 ±â€¯2,4 and tertiles 7.1 y 10.1 mL/kg/h. We divided our population according to the percentage of sessions with UFR/W above the limits described in the literature associated with increased mortality (10.0 ml/kg/h and 13.0 mL/kg/h). Patients with higher UFR/W were younger, with higher interdialytic weight gain and weight reduction percentage but lower dry, pre and post dialysis weight. Throughout the follow-up, 46 (21.4%) patients died, the majority over 70 years old, diabetic or with cardiovascular disease. There were neither differences regarding mortality between groups nor differences in UFR/W among patients who died and those who did not. Contrary to previous studies, we did not find an association between UFR/W and mortality, maybe due to a higher prevalence in the use of cardiovascular protection drugs and lower UFR/W. CONCLUSIONS: The highest UFR/W were observed in younger patients with lower weight and were not associated with an increased mortality.

Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease.

BACKGROUND: Growth Differentiation Factor-15 (GDF15) is a member of the TGF-ß superfamily. Increased serum GDF15 has been associated with increased risk of chronic kidney disease (CKD) progression. However, no prior studies have addressed the significance of urinary GDF15 in adult CKD. METHODS: We measured serum and urinary GDF15 in a prospective cohort of 84 patients who underwent kidney biopsy and assessed their association with outcomes (survival, kidney replacement therapy) during a follow-up of 29 ± 17 months. RESULTS: There was a statistically significant correlation between serum and urine GDF15 values. However, while serum GDF15 values increased with decreasing glomerular filtration rate, urinary GDF15 did not. Immunohistochemistry located kidney GDF15 expression mainly in tubular cells, and kidney GDF15 staining correlated with urinary GDF15 values. Urine GDF15 was significantly higher in patients with a histologic diagnosis of diabetic nephropathy than in diabetic patients without diabetic nephropathy. This was not the case for serum GDF15. Both serum and urine GDF15 were negatively associated with patient survival in multivariate models. However, when both urine and serum GDF15 were present in the model, lower urine GDF15 predicted patient survival [B coefficient (SEM) - 0.395 (0.182) p 0.03], and higher urine GDF15 predicted a composite of mortality or kidney replacement therapy [0.191 (0.06) p 0.002], while serum GDF15 was not predictive. Decision tree analysis yielded similar results. The area under the curve (AUC) of the receiver operating curve (ROC) for urine GDF15 as a predictor of mortality was 0.95 (95% CI 0.89-1.00, p < 0.001). CONCLUSIONS: In conclusion, urinary GDF15 is associated with kidney histology patterns, mortality and the need for renal replacement therapy (RRT) in CKD patients who underwent a kidney biopsy.

Podocyte and tubular involvement in AngioJet-induced kidney injury.

The AngioJet technique combines localized thrombolysis and percutaneous mechanical thrombectomy (PMT). However, PMT may cause acute kidney injury (AKI), which has been ascribed to severe mechanical haemolysis, although no renal biopsies have been reported. We now report the first renal biopsy in a patient with AKI following PMT. There is histological evidence of haemoglobin (Hb)-induced tubular injury and podocyte stress characterized by intracellular Hb and staining for ferritin and hemo-oxygenase-1, suggestive of an adaptive response to oxidative stress. This confirms that Hb is involved in kidney cell injury and supports the existence of several different kidney cellular targets.

Vitamin D deficiency in dialysis patients: effect of dialysis modality and implications on outcome.

OBJECTIVE: Vitamin D deficiency has been linked to cardiovascular disease and mortality in hemodialysis (HD) patients. The purpose of the present cross-sectional study was to analyze the Vitamin D status of dialysis patients from a single center, study determinants of Vitamin D deficiency, and assess its implications on outcome. METHODS: A prospective observational study of 115 prevalent dialysis patients was carried out, in which clinical and dialysis-related characteristics including routine biochemistry were studied in relation to levels of 25-hydroxyvitamin-D (25[OH]D, chemiluminescence). Survival was assessed after a median follow-up period of 413 days. RESULTS: 25(OH)D deficiency and insufficiency was present in 51% and 42% of the patients, respectively. Only 7% of the patients showed normal 25(OH)D levels. Peritoneal dialysis patients presented the lowest 25(OH)D levels. Also, a significant difference was found between on-line hemodiafiltration (OL-HDF) and conventional HD (11 [6 to 16] versus 19 [13 to 27] ng/mL; P < 0.001; 25th to 75th percentiles, conventional HD versus OL-HDF respectively). In multinomial logistic regression analysis, patients on conventional HD had 8.35 greater odds (95% CI [2.04 to 34.20]) of 25(OH)D deficiency than OL-HDF even after adjustment for sex, parathyroid hormone, pH, and Charlson comorbidity index. During the follow-up period, 18 patients died. Both crude and adjusted (hazard ratio, 6.96; 95% CI [1.44 to 33.64]) Cox analysis identified 25(OH)D deficiency as a mortality risk factor. CONCLUSION: This observational study underlines the high prevalence of hypovitaminosis D in dialysis patients and its strong implications on outcome. Furthermore, our results suggest that OL-HDF was associated with a better preservation of the vitamin D status as compared with conventional HD.

Low Intracellular Water, Overhydration, and Mortality in Hemodialysis Patients.

BACKGROUND: In hemodialysis patients, extracellular water (ECW) overload predicts all-cause and cardiovascular mortality. The primary aim of the present study was to analyze changes in post-dialysis (i.e., following removal of excess ECW) ECW, intracellular water (ICW), and the overhydration (OH) parameter over time. Additionally, the association of these parameters with mortality was explored. PATIENTS AND METHODS: Prospective study of prevalent hemodialysis patients (n = 124) followed for a median of 20 (interquartile range (IQR) 8-31) months. In three visits, inflammation (C-reactive protein) and post-dialysis fluid status (bioimpedance, BIS) were assessed. RESULTS: During follow-up, the overhydration (OH) parameter increased (-0.696 ± 1.6 vs. 0.268 ± 1.7 L; p = 0.007) at the expense of a decrease in intracellular water (ICW) (19.90 ± 4.5 vs. 18.72 ± 4.1 24 L; p = 0.006) with a non-significant numerical increase in ECW/ICW ratio (0.795 ± 0.129 vs. 0.850 ± 0.143; p = 0.055). Baseline ICW positively correlated with muscle mass and energy intake and negatively with C-reactive protein and it was lower in those who died than in survivors (15.09 ± 2.36 vs. 18.87 ± 4.52 L; p = 0.004). In Kaplan-Meier analysis, patients with low baseline ICW (≤17 L) and high ECW/ICW ratio (≥0.84) were at an increased risk of death. Baseline ICW was also associated with the risk of death in adjusted Cox proportional hazards models (HR 0.62 (0.40-0.98) p = 0.04). CONCLUSIONS: In hemodialysis patients, the post-dialysis OH parameter increased over time while ICW decreased, without changes in ECW. Low baseline post-dialysis ICW correlated with muscle wasting and inflammation and was an independent risk factor for mortality.

Clarifying the concept of chronic kidney disease for non-nephrologists.

Chronic kidney disease (CKD) expands the prior concept of chronic renal insufficiency by including patients with relatively preserved renal function, as assessed by the estimated glomerular filtration rate (eGFR), as even these early CKD stages are associated with an increased risk for all-cause death and cardiovascular death, CKD progression and acute kidney injury. A decreased eGFR (<60 mL/min/1.73 m2) is by itself diagnostic of CKD when persisting for >3 months. However, when eGFR is ≥60 mL/min/1.73 m2, an additional criterion is required to diagnose CKD. In a recent clinical trial published in The New England Journal of Medicine, all 6190 participants were reported to have CKD: 47% had Stages 1 and 2 CKD and 53% had Stage 3 CKD. This illustrates a widespread misunderstanding of the concept of CKD. Moreover, CKD categories in this study were assigned based on the estimated creatinine clearance. Since both estimated creatinine clearance and creatinine clearance overestimate eGFR, this illustrates another frequent misunderstanding: equating GFR with creatinine clearance. In this commentary, we clarify the concept of CKD and of CKD categories for non-nephrologists. Assigning a diagnosis of CKD to a patient with normal renal function and absence of other evidence of CKD may have negative consequences for the individual (e.g. insurance and others) as well as for the medical community at large by creating confusion about the concept.