Oral hydration as a safe prophylactic measure to prevent post-contrast acute kidney injury in oncologic patients with chronic kidney disease (IIIb) referred for contrast-enhanced computed tomography: subanalysis of the oncological group of the NICIR study.

BACKGROUND: T he objective of this study is to evaluate oral hydration compared to intravenous (i.v.) hydration in the prevention of post-contrast acute kidney injury (PC-AKI) in the oncologic subgroup of patients with stage IIIb chronic kidney disease (CKD) included in the NICIR study referred for elective contrast-enhanced computed tomography (CE-CT). MATERIAL AND METHODS: We performed a retrospective subanalysis of the oncological subgroup (174/228 patients, 74%) from a continuous prospective database of patients included in the recently published non-inferiority NICIR study. Patients received prophylaxis against PC-AKI with either oral hydration (500 mL of water 2 h before and 2000 mL during the 24 h after CE-CT) or i.v. hydration (sodium bicarbonate (166 mmol/L) 3 mL/kg/h starting 1 h before and 1 mL/kg/h during the first hour after CE-CT). The primary outcome was to compare the proportion of PC-AKI in the first 48 to 72 h after CE-CT in the two hydration groups. Secondary outcomes were to compare persistent PC-AKI, the need for haemodialysis, and the occurrence of adverse events related to prophylaxis in each group. RESULTS: Of 174 patients included in the subanalysis, 82 received oral hydration and 92 received i.v. hydration. There were no significant differences in clinical characteristics or risk factors between the two study arms. Overall the PC-AKI rate was 4.6% (8/174 patients), being 3.7% in the oral hydration arm (3/82 patients) and 5.4% (5/92 patients) in the i.v. hydration arm. The persistent PC-AKI rate was 1.2% (1/82 patients) in the oral hydration arm and 3.3% (3/92 patients) in the i.v. hydration arm. No patient required dialysis during the first month after CE-CT or had adverse effects related to the hydration regime. CONCLUSION: In oncological patients with stage IIIb CKD referred for elective CE-CT, the rate of PC-AKI in those receiving oral hydration did not significantly differ from that of patients receiving i.v. hydration.

Incidence of erythropoietin antibody-mediated pure red cell aplasia: the Prospective Immunogenicity Surveillance Registry (PRIMS).

BACKGROUND: Subcutaneous administration of Eprex(®) (epoetin alfa) in patients with chronic kidney disease (CKD) was contraindicated in the European Union between 2002 and 2006 after increased reports of anti-erythropoietin antibody-mediated pure red cell aplasia (PRCA). The Prospective Immunogenicity Surveillance Registry (PRIMS) was conducted to estimate the incidence of antibody-mediated PRCA with subcutaneous administration of a new coated-stopper syringe presentation of Eprex(®) and to compare this with the PRCA incidence with subcutaneous NeoRecormon(®) (epoetin beta) and Aranesp(®) (darbepoetin alfa). METHODS: PRIMS was a multicentre, multinational, non-interventional, parallel-group, immunogenicity surveillance registry. Adults with CKD receiving or about to initiate subcutaneous Eprex(®), NeoRecormon(®) or Aranesp(®) for anaemia were enrolled and followed for up to 3 years. Unexplained loss or lack of effect (LOE), including suspected PRCA, was reported, with antibody testing for confirmation of PRCA. RESULTS: Of the 15 333 patients enrolled, 5948 received Eprex(®) (8377 patient-years) and 9356 received NeoRecormon(®)/Aranesp(®) (14 286 patient-years). No treatment data were available for 29 patients. Among 23 patients with LOE, five cases of PRCA were confirmed (Eprex(®), n = 3; NeoRecormon(®), n = 1; Aranesp(®), n = 1). Based on exposed time, PRCA incidence was 35.8/100 000 patient-years (95% CI 7.4-104.7) for Eprex(®) versus 14.0/100 000 patient-years (95% CI 1.7-50.6) for NeoRecormon(®)/Aranesp(®). The incidence of PRCA with Eprex(®) was not significantly different versus comparator ESAs (rate ratio: 2.56; 95% CI 0.43-15.31). An analysis based on observed time produced similar findings. CONCLUSION: This large, prospective registry demonstrates that PRCA is rare with subcutaneous administration of either the new coated-stopper syringe presentation of Eprex(®), or NeoRecormon(®) or Aranesp(®).

A comparison of calcium acetate/magnesium carbonate and sevelamer-hydrochloride effects on fibroblast growth factor-23 and bone markers: post hoc evaluation from a controlled, randomized study.

BACKGROUND: Different phosphate binders exert differing effects on bone mineral metabolism and levels of regulating hormones. The objective of this post hoc evaluation of the CALcium acetate MAGnesium carbonate (CALMAG) study was to compare the effects of calcium acetate/magnesium carbonate (CaMg) and a calcium-free phosphate binder, sevelamer-hydrochloride (HCl), on serum levels of fibroblast growth factor-23 (FGF-23) and markers of bone turnover. METHODS: This secondary analysis of the controlled, randomized CALMAG study, comparing the effect of CaMg and sevelamer-HCl on serum phosphorus (P), aimed to investigate the parameters described above. The analysis included 204 patients who completed the initial study per protocol (CaMg, n = 105; sevelamer-HCl, n = 99). RESULTS: The study showed that serum levels of FGF-23 were significantly reduced with CaMg and sevelamer-HCl, with no difference between groups at Week 25 [analysis of covariance (ANCOVA); log-intact FGF-23 (iFGF-23), P = 0.1573]. FGF-23 levels strongly correlated with serum P levels at all time points in both groups. The bone turnover parameters alkaline phosphatase (AP), bone AP (BAP), procollagen type 1 amino-terminal propeptide 1 (P1NP), osteoprotegerin (OPG), beta-crosslaps (ß-CTX) and tartrate-resistant acid phosphatase 5b (TRAP 5b) increased significantly in the sevelamer-HCl group; they remained almost unchanged in the CaMg group, after the initial phase of P lowering (ANCOVA, P < 0.0001 for all except OPG, P = 0.1718). CONCLUSIONS: CaMg and sevelamer-HCl comparably lower serum levels of iFGF-23. Changes in bone parameters were dependent on characteristics of the phosphate binder; in contrast with sevelamer-HCl, CaMg had no influence on bone turnover markers.

Adverse renal effects of check-point inhibitors (ICI) in cancer patients: Recommendations of the Onco-nephrology Working Group of the Spanish Society of Nephrology.

The most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of Onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in Onconephrology consultations.

Paricalcitol reduces oxidative stress and inflammation in hemodialysis patients.

BACKGROUND: Treatment with selective vitamin D receptor activators such as paricalcitol have been shown to exert an anti-inflammatory effect in patients on hemodialysis, in addition to their action on mineral metabolism and independently of parathyroid hormone (PTH) levels. The objective of this study was to evaluate the additional antioxidant capacity of paricalcitol in a clinical setting. METHODS: The study included 19 patients with renal disease on hemodialysis, of whom peripheral blood was obtained for analysis at baseline and three months after starting intravenous paricalcitol treatment. The following oxidizing and inflammatory markers were quantified: malondialdehyde (MDA), nitrites and carbonyl groups, indoleamine 2,3-dioxygenase (IDO), tumor necrosis factor alfa (TNF-α), interleukin-6 (IL-6), interleukin-18 (IL-18) and C-reactive protein (CRP). Of the antioxidants and anti-inflammatory markers, superoxide dismutase (SOD), catalase, reduced glutathione (GSH), thioredoxin, and interleukin-10 (IL-10) levels were obtained. RESULTS: Baseline levels of oxidation markers MDA, nitric oxide and protein carbonyl groups significantly decreased after three months on paricalcitol treatment, while levels of GSH, thioredoxin, catalase and SOD activity significantly increased. After paricalcitol treatment, levels of the inflammatory markers CRP, TNF-α, IL-6 and IL-18 were significantly reduced in serum and the level of anti-inflammatory cytokine IL-10 was increased. CONCLUSIONS: In renal patients undergoing hemodialysis, paricalcitol treatment significantly reduces oxidative stress and inflammation, two well known factors leading to cardiovascular damage.

An epidemiological study of hemodialysis patients based on the European Fresenius Medical Care hemodialysis network: results of the ARO study.

BACKGROUND/AIMS: ARO, an observational study of hemodialysis (HD) patients in Europe, aims to enhance our understanding of patient characteristics and practice patterns to improve patient outcome. METHODS: HD patients (n = 8,963) from 134 Fresenius Medical Care facilities treated between 2005 and 2006 were randomly selected from 9 European countries (Czech Republic, France, Hungary, Italy, Poland, Portugal, Spain, Slovak Republic and Slovenia) and Turkey. Information was captured on demographics, comorbidities, medications, laboratory and dialysis parameters, and outcome. RESULTS: Patients were followed for 1.4 ± 0.7 years. Wide variation by country was observed for age, sex and diabetes as a cause of chronic kidney disease. Cardiovascular disease was present in 73% of patients. Dialysis parameters were homogeneous across countries. Arteriovenous fistulas were frequently used (73%). More incident patients had hemoglobin <11 g/dl than prevalent patients (50 vs. 33%, respectively). Phosphatemia and intact parathyroid hormone were similar between incident and prevalent patients (4.7 ± 1.2 mg/dl and 190 vs. 213 ng/l, respectively). Medication use varied widely by country. In total, 5% of patients underwent renal transplantation. Overall death rate was 124/1,000 patient-years. CONCLUSION: ARO revealed differences in HD practice patterns and patient characteristics in the 10 participating countries. Future ARO studies will fill gaps in the knowledge about the care of European HD patients.

Monographic consultation of onconephrology. Rationale and implementation.

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in Onconephrology could improve the care of these patients. Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of Onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology., together with the experience of two Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations.

Monographic consultation of onconephrology. Rationale and implementation. / Consulta monográfica de onconefrología. Justificación y puesta en marcha.

The increase in demand for medical care for renal complications associated with neoplastic diseases is a reality in most nephrology departments. In response to this overall situation, the creation of healthcare models such as monographic consultations and develop training programs in onconephrology could improve the care of these patients. Through an exploratory and descriptive study, we identified current situation of kidney involvement in cancer patients. The objective of the present study is to establish the criteria for specific assistance in the field of onconephrology. For this, we have reviewed key aspects and analyzed the current situation in our country, through a survey addressed to all nephrologists through the Spanish Society of Nephrology, together with the experience of 2 Spanish centers. From this information, we have established some requirements and recommendations for the start-up of these consultations.

Real-world safety and effectiveness of sucroferric oxyhydroxide for treatment of hyperphosphataemia in dialysis patients: a prospective observational study.

BACKGROUND: The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis. METHODS: This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels. RESULTS: The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: -1.0 mg/dL, P < 0.01). Percentage of patients achieving serum phosphorus ≤4.5 mg/dL increased from 12.0% at BL to 34.8% at Month 30, while the percentage achieving serum phosphorus ≤5.5 mg/dL increased from 29.9% to 63.0%. CONCLUSIONS: SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.

Evaluation of calcium acetate/magnesium carbonate as a phosphate binder compared with sevelamer hydrochloride in haemodialysis patients: a controlled randomized study (CALMAG study) assessing efficacy and tolerability.

BACKGROUND: Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option. METHODS: This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups. RESULTS: Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events. CONCLUSION: CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis.

BACKGROUND: Secondary hyperparathyroidism is observed in patients with early chronic kidney disease (CKD). This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis. STUDY DESIGN: Double-blind, randomized, 32-week, phase 3 study. SETTING & PARTICIPANTS: 404 participants with stage 3 or 4 CKD from 73 centers in 9 countries. INTERVENTIONS: Cinacalcet:placebo (3:1 ratio). OUTCOMES & MEASUREMENTS: Proportion of participants with a mean decrease of 30% or greater in intact parathyroid hormone (iPTH) level, proportion with iPTH level of 70 or less or 110 or less pg/mL (stage 3 and 4 CKD, respectively), and mean percentage of iPTH change from baseline, all during the efficacy-assessment phase. RESULTS: A greater proportion of cinacalcet than placebo participants achieved a 30% or greater decrease in iPTH level (74% versus 28%; P < 0.001), corresponding to a 43.1% decrease in iPTH level from baseline (cinacalcet) compared with a 1.1% increase (placebo). At week 32, serum calcium levels were 8.9 +/- 0.8 mg/dL (-8.9%; cinacalcet) and 9.9 +/- 0.6 mg/dL (+0.8%; placebo), phosphorus levels were 4.5 +/- 1.0 mg/dL (+21.4%) and 4.0 +/- 0.7 mg/dL (+6.8%), and calcium-phosphorus product values were 40.1 +/- 8.3 mg(2)/dL(2) (+18.9%) and 38.9 +/- 6.9 mg(2)/dL(2) (+17.1%), respectively. During the study course, 62% (cinacalcet) and 1% (placebo) of participants experienced 2 consecutive serum calcium concentrations less than 8.4 mg/dL. They generally were asymptomatic and without significant clinical consequences. Treatment generally was well tolerated, and most adverse events were mild to moderate in severity. LIMITATIONS: The study was not designed to assess the effects of cinacalcet on vascular calcification, bone histomorphometric parameters, or other clinical outcomes. It is not known whether the observed differences in changes in iPTH levels are clinically more important than observed differences in changes in serum calcium or phosphorus levels or dosages of vitamin D sterols and phosphate binders. CONCLUSIONS: These data show that cinacalcet treatment in patients with CKD not receiving dialysis can decrease plasma iPTH levels, but with frequent (albeit generally asymptomatic) serum calcium levels less than 8.4 mg/dL and increases in serum phosphorus levels.

Onco-Nephrology: Cancer, chemotherapy and kidney. / Onco-Nefrología: cáncer, quimioterapia y riñón.

Chronic kidney disease (CKD), cancer and haematological diseases share areas of reciprocal influence. Cancer can affect the kidney either as glomerular lesions or as a result of the toxic effects of medication or radiation with acute (thrombotic microangiopathy, acute kidney injury, interstitial nephropathies among others) or chronic processes (worsening of CKD after nephrectomy due to renal cancer, interstitial fibrosis, hydroelectrolytic disorders). On the other hand, patients who require renal replacement therapy with dialysis and particularly with kidney transplantation are at high risk of onset of cancer due to the immunosuppression situation that they generate. In addition to conventional chemotherapy, innovative treatments have been developed: target agents against growth factors and their receptor; anti-angiogenic drugs; immunoregulatory proteins; cell cycle regulators; and enzyme inhibitors. Other immunotherapeutic approaches have also been developed, such as vaccines, adoptive cell therapy (CAR T cells) or development of antibodies. All these therapeutic advances will improve the outcomes against cancer and haematological diseases, but they are not free from secondary renal problems. Onco-Nephrology is already an important area for the Spanish Society of Nephrology with a large number of inter-consultations. Nephrologists need a better understanding of rapidly evolving areas of cancer biology and its treatment in order to become valued members of the cancer care team and to provide the best nephrology care possible.

Maintenance of target hemoglobin level in stable hemodialysis patients constitutes a theoretical task: a historical prospective study.

Maintenance of target hemoglobin (Hb) values in hemodialysis patients treated with erythropoiesis-stimulating agents (ESAs) remains difficult. We examined Hb variability in the clinical setting in hemodialysis patients. Hemodialysis patients treated with ESAs who maintained the recommended Hb range of 11-13 g per 100 ml over 3 months and were not admitted to hospital, did not require transfusion, and did not experience any major clinical event during this period were followed prospectively for 1 year. Anemia events, Hb variation events (any value out of +/-1.5 g per 100 ml of the median Hb level in the total follow-up period for the individual patient), risk factors for anemia, and Hb variation events were assessed. We studied 420 patients (63% males, mean age 61 years), 222 received short-acting erythropoietin (EPO) and 198 long-acting darbepoetin. A total of 4654 blood samples (mean 11.1 per patient-year) were analyzed. Only 3.8% of patients were maintained within the target Hb levels (11-13 g per 100 ml) during 1 year. Hb variation events occurred in 20.8% of laboratory values and anemia events in 14.7%, with a median time to the first event of 3 months. Treatment with short-acting EPO (vs long-acting darbepoetin), change of ESA dose in the previous visit, resistance index, and hospitalization were significant risk factors for both anemia events and Hb variation events. Our results show that Hb values are rarely maintained within the recommended guidelines even in more stable hemodialysis patients. Hb variability is frequently associated with clinical events or ESA dose changes. Long-acting darbepoetin achieved better Hb stability than short-acting EPO.

Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet.

BACKGROUND: The parathyroid-calcium (Ca(2+)-PTH) curve expresses modulation of parathyroid hormone (PTH) secretion by the parathyroid gland as a function of changing extracellular Ca(2+) concentration. Patients with hyperparathyroidism (HPT) show a rightward shift of the curve compared with controls, suggesting a reduced sensitivity of parathyroid cells to Ca(2+). Increasing the sensitivity of the parathyroid gland to extracellular Ca(2+) by manipulation of the Ca(2+)-sensing receptor (CaR) may have therapeutic potential. Calcimimetics allosterically modify CaR and render it more sensitive to extracellular Ca(2+), accounting for the simultaneous reduction of Ca(2+) and PTH seen in most patients. METHODS: The Ca(2+)-PTH curve was evaluated in 10 haemodialysis patients, with baseline intact PTH levels >300 pg/ml in two haemodialysis sessions, one before and the other after (range, 9-22 weeks) cinacalcet treatment. In each session a 2-h low-dialysate Ca(2+) concentration was used to induce hypocalcaemia and maximally stimulate PTH secretion, followed immediately by a 2-h high-dialysate Ca(2+) concentration to induce hypercalcaemia and maximally inhibit PTH secretion. RESULTS: Significant decreases in ionized Ca(2+) and intact PTH were observed following cinacalcet treatment. Cinacalcet treatment also led to a decrease in the set point for Ca(2+) and to a leftward shift of the Ca(2+)-PTH curve. Significant differences were present in all segments of the Ca(2+)-PTH curves. CONCLUSION: The pathological rightward shift of the Ca(2+)-PTH curve seen in many HPT patients may be reversed by cinacalcet treatment.

Proton Pump Inhibitor Usage and the Risk of Mortality in Hemodialysis Patients.

INTRODUCTION: Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. METHODS: We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score-matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. RESULTS: PPI use was associated with hypomagnesemia (Mg <1.8 mg/dl (0.75 mmol/l); odds ratio [OR] = 2.70, 95% confidence interval [CI] = 1.38-5.27, P < 0.01). The exposure to PPIs in the full patient cohort was identified as an independent predictor for all-cause mortality in both univariate (HR = 3.16, 95% CI = 1.69-5.90, P < 0.01) and multivariate (HR = 2.70, 95% CI = 1.38-5.27, P < 0.01) Cox regression models. Moreover PPI use was identified as a predictor of CV mortality (HR = 1.51, 95% CI = 1.05-2.20, P = 0.03) Of the 820 patients matched throughout the propensity score analysis, the hazard ratios for all-cause mortality (HR = 1.412, 95% CI = 1.04-1.93, P = 0.03) and CV mortality (HR = 1.67, 95% CI = 1.03-2.71, P = 0.04) were higher among patients on PPIs versus those not on PPIs. CONCLUSION: The study data suggest that the PPI treatment should be regularly monitored and prescribed only when indicated.

Efectos renales adversos por inhibidores del check-point (ICP) en pacientes con cáncer. Recomendaciones del grupo de Onconefrología de la Sociedad Española de Nefrología (SEN) / Adverse renal effects of check-point inhibitors (ICI) in cancer patients: Recommendations of the Onco-nephrology Working Group of the Spanish Society of Nephrology

El enfoque más utilizado en el tratamiento inmunoterápico del cáncer es la administración de anticuerpos monoclonales dirigidos contra moléculas reguladoras del control inmunitario que inhiben la activación de las células T, los llamados inhibidores del check-point (ICP). La epidemiología y patología de la nefrotoxicidad por los ICP, su diagnóstico con o sin biopsia renal, el tipo y la duración del tratamiento, la posibilidad de retratar después del daño renal, y su indicación en pacientes con cáncer y trasplante renal son ciertamente controvertidas. En ausencia de estudios definitivos, este documento está destinado a concretar unas recomendaciones consensuadas por el grupo de expertos de Onconefrología de la SEN en aquellas áreas relacionadas con la nefrotoxicidad por los ICP, con la finalidad de ayudar en la toma de decisiones en la práctica clínica diaria de las consultas de Onconefrología. (AU)

The most widely used approach in the immunotherapy treatment of cancer is the administration of monoclonal antibodies directed against regulatory molecules of immune control that inhibit the activation of T cells, the so-called check point inhibitors (ICI). ICI nephrotoxicity epidemiology and pathology; its diagnosis with or without kidney biopsy; the type and duration of treatment; the possibility of rechallenging after kidney damage; and its indication in patients with cancer and renal transplantation are certainly controversial. In the absence of definitive studies, this document is intended to specify some recommendations agreed by the group of onconephrology experts of the Spanish Society of Nephrology in those areas related to ICI nephrotoxicity, in order to help decision-making in daily clinical practice in onconephrology consultations. (AU)

Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis.

BACKGROUND: Treatment of secondary hyperparathyroidism with vitamin D and calcium in patients receiving dialysis is often complicated by hypercalcemia and hyperphosphatemia, which may contribute to cardiovascular disease and adverse clinical outcomes. Calcimimetics target the calcium-sensing receptor and lower parathyroid hormone levels without increasing calcium and phosphorus levels. We report the results of two identical randomized, double-blind, placebo-controlled trials evaluating the safety and effectiveness of the calcimimetic agent cinacalcet hydrochloride. METHODS: Patients who were receiving hemodialysis and who had inadequately controlled secondary hyperparathyroidism despite standard treatment were randomly assigned to receive cinacalcet (371 patients) or placebo (370 patients) for 26 weeks. Once-daily doses were increased from 30 mg to 180 mg to achieve intact parathyroid hormone levels of 250 pg per milliliter or less. The primary end point was the percentage of patients with values in this range during a 14-week efficacy-assessment phase. RESULTS: Forty-three percent of the cinacalcet group reached the primary end point, as compared with 5 percent of the placebo group (P<0.001). Overall, mean parathyroid hormone values decreased 43 percent in those receiving cinacalcet but increased 9 percent in the placebo group (P<0.001). The serum calcium-phosphorus product declined by 15 percent in the cinacalcet group and remained unchanged in the placebo group (P<0.001). Cinacalcet effectively reduced parathyroid hormone levels independently of disease severity or changes in vitamin D sterol dose. CONCLUSIONS: Cinacalcet lowers parathyroid hormone levels and improves calcium-phosphorus homeostasis in patients receiving hemodialysis who have uncontrolled secondary hyperparathyroidism.

Challenges and future of renal replacement therapy.

Renal community increasingly recognizes the challenges of very high mortality, morbidity and low quality of life among dialysis patients. Current hemodialysis (HD) schedule provides less than 10% of the clearance power of the natural kidneys and therefore current standard HD treatment is still a long way from providing adequate renal replacement. In the future it would be expected to improve dialysis control with the development of new technology: membranes, dialysate buffer, electrolyte concentration, system interface, arteriovenous access monitoring. Online technology must be adapted to routine HD for new prescription monitoring such as creatinine online sensing technology, sodium-specific electrode or hydrogen ion concentration. Online convective therapies offer the opportunity for a more biological renal replacement therapy increasing convective transport in order to "reproduce" glomerular function and improving small and middle molecular clearance in an economically feasible and safe way. The paradigm of thrice-weekly dialysis is faced with diminishing returns, with the possible exception of long dialysis sessions. More frequent (daily) dialysis represents a very promising tool for improving dialysis outcomes and quality of life. Future technologies for renal replacement include bioartificial kidneys based in continuous hemofiltration and bioartificial tubules. Although Phase I/II clinical trial on 10 patients with acute renal failure has been reported the procedure requires further evaluation. Organogenesis, therapeutic cloning, or cloning and organogenesis combined might in the future produce a functional and histocompatible kidney. The continuous increase in incidence and prevalence of renal-replacement therapy is a world-wide phenomenon, although the rates in Europe are still much lower than in the U.S. The increase in rates applies especially to older patients, patients with diabetes mellitus and renal vascular disease and the consequences of this important comorbidity are very important in terms of mortality.

The renal benefits of a healthy lifestyle.

Over the next decade, the number of patients with end-stage renal disease requiring treatment by dialysis may double, and even developed nations will have difficulty coping with this alarming increase. There is an urgent need to highlight the importance of modifiable risk factors as a basis for treatment strategies to prevent the development and progression of chronic kidney disease (CKD). This should include active extension of our current understanding of a healthy lifestyle.