[Recurrent atypical hemolytic uremic syndrome after renal transplantation: treatment with eculizumab]. / Síndrome urémico hemolítico atípico recurrente post-trasplante renal: tratamiento con eculizumab.

Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality. Mutations associated with factor H, factor B and complement C3 show the worst prognosis. Even though plasma therapy is occasionally useful, eculizumab is effective both for treatment and prevention of post-transplant recurrence. We describe here an adult case of congenital aHUS (C3 mutation) under preventive treatment with eculizumab after renal transplantation, with neither disease recurrence nor drug-related adverse events after a 36-months follow-up.

[Inadequate doses of hemodialysis. Predisposing factors, causes and prevention]. / Dosis de hemodiálisis subóptima. Factores predisponentes, causas y prevención.

Patients receiving sub-optimal dose of hemodialysis have increased morbidity and mortality. The objectives of this study were to identify predisposing factors and causes of inadequate dialysis, and to design a practical algorithm for the management of these patients. A cross-sectional study was conducted. Ninety patients in chronic hemodialysis at Hospital Privado Universitario de Córdoba were included, during September 2015. Twenty two received sub-optimal dose of hemodialysis. Those with urea distribution volume (V) greater than 40 l (72 kg body weight approximately) are 11 times more likely (OR = 11.6; CI 95% = 3.2 to 51.7, p < 0.0001) to receive an inadequate dose of hemodialysis, than those with a smaller V. This situation is more frequent in men (OR = 3.5; 95% CI 1.01-15.8; p = 0.0292). V greater than 40 l was the only independent predictor of sub-dialysis in the multivariate analysis (OR = 10.3; 95% CI 2.8-37; p < 0.0004). The main cause of suboptimal dialysis was receiving a lower blood flow (Qb) than the prescribed (336.4 ± 45.8 ml/min vs. 402.3 ± 28.8 ml/min respectively, p < 0.0001) (n = 18). Other causes were identified: shorter duration of the session (n = 2), vascular access recirculation (n = 1), and error in the samples (n = 1). In conclusion, the only independent predisposing factor found in this study for sub-optimal dialysis is V greater than 40 l. The main cause was receiving a slower Qb than prescribed. From these findings, an algorithm for the management of these patients was developed.

[The role of kidney transplantation in reducing mortality in a chronic dialysis program]. / Trasplante renal y disminución de la mortalidad en los programas de diálisis crónica.

For patients with chronic renal failure (CRF), kidney transplant (KT) is a better alternative to dialysis in terms of survival, life quality and costs. We studied the general characteristics, causes and survival rate of the dialysis population in 2010. We evaluated broader criteria for acceptance of transplants has affected the results of the procedure in that period. A total of 118 dialysis patients were included; mean age 56.9 ± 18.4 years, dialysis duration 45.5 ± 59.6 months, main cause of CRF was diabetes in 35 (30%), and 58 (49%) were included in waiting list for KT. Of the 34 patients who finished dialysis in 2010, 18 (53%) were KT, while 12 (35%) died (cardiovascular 50%, infectious 17%). Survival at 12 months was 85% for the total group, 98% on waiting list and 72% those who were not enrolled. During 2010 there were 88 KT, 62 with cadaveric donors (CD), 18 with living donors and 8 with double pancreas-kidney transplants. Recipients of CD were 50.7 years old, with 67 months on dialysis, 8 (13%) diabetics, and 12 (20%) with previous KT. Donors had a mean age of 45 years, 28 (45%) expanded criteria, and 27.7 hours of cold ischemia time. During an approximate follow-up of 11.4 months, 13 (21%) suffered acute graft rejection, survival was 88% for graft and 93% for patients. We emphasize KT as the main cause of success as regards dialysis. No differences in risk factors were found to significantly affect graft or patient survival.

Systemic autoinflammatory disease, IgA glomerulonephritis and renal cortical necrosis: coincidence or causation?

We present a patient with a rare systemic autoinflammatory disease (mevalonate kinase deficiency -MKD-) with the identification of two heterozygous variants (c.1129G>A and c.32C>T) in the Mevalonate Kinase gene, detected by next generation sequencing and a highly prevalent glomerulonephritis (IgA nephropathy). The patient presents clinically with a monthly recurrent periodic fever from 12 days of age, accompanied by mucocutaneous lesions (maculopapular rash in extremities, aphthous stomatitis), joint (arthralgias in ankles, wrists and knees), lymphoid (cervical lymphadenopathy, splenomegaly), gastrointestinal (diarrhea, abdominal pain) and kidney (hematuria and proteinuria) with repeated biopsies showing IgA nephropathy alternating activity with chronicity. During follow-up. The patients presented a poor therapeutic response to multiple immunosuppressive regimens used for 7 years (corticosteroids, azathioprine, mycophenolate, cyclophosphamide, rituximab and tocilizumab), and finally a good response to canakinumab. Four years after starting canakinumab, during the course of an infection due to a muscle abscess, the clinical presentation is complicated by a severe renal microvascular event (renal cortical necrosis -RCN-) with acute kidney injury and dialysis requirement. Therecurrent episodes of inflammation due to MKD could act as triggers for the reactivation of glomerulonephritis (which would explain the poor response to immunosuppressants and the rapid progression to histological chronicity) and to generate a microenvironment that predisposes the development of RCN in the face of a non-serious infection. A defect in IgA molecules has been described in MKD, a phenomenon also observed in IgA nephropathy. This raises the challenging hypothesis of a common pathogenetic link between all the patient's clinical manifestations.

Presentamos un paciente con una rara enfermedad autoinflamatoria sistémica (deficiencia de mevalonato quinasa -DMQ-) con la identificación de dos variantes heterocigotas (c.1129G>A y c.32C>T) en el gen Mevalonato Quinasa, detectadas por secuenciación masiva en paralelo y una glomerulonefritis de alta prevalencia (nefropatía por IgA). El paciente presentó un cuadro de fiebre periódica recurrente mensual desde los 12 días de vida, acompañada de lesiones mucocutáneas (rash maculopapular en extremidades, estomatitis aftosa), compromiso articular (artralgias en tobillos, muñecas y rodillas), linfoideo (linfoadenopatía cervical, esplenomegalia), gastrointestinal (diarrea, dolor abdominal) y renal (hematuria y proteinuria) con repetidas biospias mostrando nefropatía por IgA alternando actividad y cronicidad. Durante el seguimiento, tuvo una pobre respuesta terapéutica a múltiples esquemas inmunosupresores utilizados durante 7 años (corticoides, azatrioprina, micofenolato, ciclofosfamida, rituximab y tocilizumab), y buena respuesta finalmente a canakinumab. Cuatro años posteriores al inicio de canakinumab, durante el curso de una infección por un absceso muscular, el cuadro clínico se complica con un evento microvascular renal grave (necrosis cortical renal -NCR-) con fallo renal agudo y necesidad de diálisis. Los episodios recurrentes de inflamación por la DMQ podrían actuar como gatillos para la reactivación de su glomerulonefritis (lo que explicaría la escasa respuesta a inmunosupresores y la progresión rápida a cronicidad histológica) y para generar un microambiente que predisponga el desarrollo de una NCR ante una infección no grave. En la DMQ se ha descripto un defecto en las moléculas de IgA, fenómeno también observado en la nefropatía por IgA. Esto plantea la desafiante hipótesis de un vínculo patogénico común entre todas las manifestaciones clínicas del paciente.

Inhibition of MTOR disrupts autophagic flux in podocytes.

Inhibitors of the mammalian target of rapamycin (MTOR) belong to a family of drugs with potent immunosuppressive, antiangiogenic, and antiproliferative properties. De novo or worsening proteinuria can occur during treatment with these agents, but the mechanism by which this occurs is unknown. We generated and characterized mice carrying a podocyte-selective knockout of the Mtor gene. Although Mtor was dispensable in developing podocytes, these mice developed proteinuria at 3 weeks and end stage renal failure by 5 weeks after birth. Podocytes from these mice exhibited an accumulation of the autophagosome marker LC3 (rat microtubule-associated protein 1 light chain 3), autophagosomes, autophagolysosomal vesicles, and damaged mitochondria. Similarly, human podocytes treated with the MTOR inhibitor rapamycin accumulated autophagosomes and autophagolysosomes. Taken together, these results suggest that disruption of the autophagic pathway may play a role in the pathogenesis of proteinuria in patients treated with MTOR inhibitors.

[Associated factors and clinical implications of post transplant renal anemia]. / Factores asociados y consecuencias clínicas de la anemia post trasplante renal.

A considerable percentage of patients exhibit anemia post kidney transplant. Its origin is multifactorial and the main causes involved depend on the post transplant period considered. We studied in a group of 134 consecutive patients the associated factors and the clinical implications of "late anemia" (6 months post transplant). Multiple regression analysis showed that post transplant oliguria and acute rejection episodes were significantly associated with anemia. Graft survival at 36 months was significantly reduced in the anemic group (83 % versus 96%, p < 0.01). No differences in patients survival or rate of cardiovascular events were observed. We concluded that anemia at 6 months post transplant is independently and significantly associated with events that reduced functioning renal mass and kidney survival.

Estimation of Glomerular Filtration Rate in Obese Patients: Utility of a New Equation.

There is no consensus on the best equation to estimate glomerular filtration rate (eGFR) in obese patients (OP). Objective: to evaluate the performance of the current equations and the new Argentinian Equation ("AE") to estimate GFR in OP. Two validation samples were used: internal (IVS, using 10-fold cross-validation) and temporary (TVS). OP whose GFR was measured (mGFR) with clearance of iothalamate between 2007/2017 (IVS, n = 189) and 2018/2019 (TVS, n = 26) were included. To evaluate the performance of the equations we used: bias (difference between eGFR and mGFR), P30 (percentage of estimates within ±30% of mGFR), Pearson's correlation (r) and percentage of correct classification (%CC) according to the stages of CKD. The median age was 50 years. Sixty percent had grade I obesity (G1-Ob), 25.1% G2-Ob and 14.9% G3-Ob, with a wide range in mGFR (5.6-173.1 mL/min/1.73 m2). In the IVS, AE obtained a higher P30 (85.2%), r (0.86) and %CC (74.4%), with lower bias (-0.4 mL/min/1.73 m2). In the TVS, AE obtained a higher P30 (88.5%), r (0.89) and %CC (84.6%). The performance of all equations was reduced in G3-Ob, but AE was the only one that obtained a P30 > 80% in all degrees. AE obtained better overall performance to estimate GFR in OP and could be useful in this population. Conclusions from this study may not be generalizable to all populations of obese patients since they were derived from a study in a single center with a very specific ethnic mixed population.

Optimised versus standard automated peritoneal dialysis regimens pilot study (OptiStAR): A randomised controlled crossover trial.

BACKGROUND: The continuous global rise of end-stage kidney disease creates a growing demand of economically beneficial home-based kidney replacement therapies such as peritoneal dialysis (PD). However, undesirable absorption and exposure of peritoneal tissues to glucose remain major limitations of PD. METHODS: We compared a reference (standard) automated PD regimen 6 × 2 L 1.36% glucose (76 mmol/L) over 9 h with a novel, theoretically glucose sparing (optimised) prescription consisting of 'ultrafiltration cycles' with high glucose strength (126 mmol/L) and 'clearance cycles' with ultra-low, physiological glucose (5 mmol/L) for approximately 40% of the treatment time. Twenty-one prevalent PD patients underwent the optimised regimen (7 × 2 L 2.27% glucose + 5 × 2 L 0.1% glucose over 8 h) and the standard regimen in a crossover fashion. Six patients were excluded from data analysis. RESULTS: Median glucose absorption was 43 g (IQR 41-54) and 44 g (40-55) for the standard and optimised intervention, respectively (p = 1). Ultrafiltration volume, weekly Kt/V creatinine and urea were significantly improved during optimised interventions, while no difference in sodium removal was detected. Post hoc analysis showed significantly improved ultrafiltration efficiency (ml ultrafiltration per gram absorbed glucose) during optimised regimens. No adverse events were observed except one incidence of drain pain. CONCLUSION: Optimised treatments were feasible and well tolerated in this small pilot study. Despite no difference in absorbed glucose, results indicate possible improvements of ultrafiltration efficiency and small solute clearances by optimised regimens. Use of optimised prescriptions as glucose sparing strategy should be evaluated in larger study populations.

High-dose steroid treatment increases free water transport in peritoneal dialysis patients.

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m(2)). As compared with pre-transplantation values, the post-transplantation test revealed an ∼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gene.

SGLT2 inhibition does not reduce glucose absorption during experimental peritoneal dialysis.

INTRODUCTION: Unwanted glucose absorption during peritoneal dialysis (PD) remains a clinical challenge, especially in diabetic patients. Recent experimental data indicated that inhibitors of the sodium and glucose co-transporter (SGLT)-2 could act to reduce glucose uptake during PD, which raises the question of whether glucose absorption may also occur via intracellular or trans-cellular pathways. METHODS: We performed PD in anesthetized Sprague-Dawley rats using a fill volume of 20 mL with either 1.5% glucose fluid or 4.25% glucose fluid for 120 min dwell time to evaluate the effects of SGLT2 inhibition by empagliflozin on peritoneal water and solute transport. To assess the diffusion capacity of glucose, we developed a modified equation to measure small solute diffusion capacity, taking convective- and free water transport into account. RESULTS: SGLT2 inhibition markedly increased the urinary excretion of glucose and lowered plasma glucose after PD compared to sham groups. Glucose absorption for 1.5% glucose was 165 mg 95% CI (145-178) in sham animals and 157 mg 95% CI (137-172) for empagliflozin-treated animals. For 4.25% glucose, absorption of glucose was 474 mg 95% CI (425-494) and 472 mg 95% CI (420-506) for sham and empagliflozin groups, respectively. No significant changes in the transport of sodium or water across the peritoneal barrier could be detected. CONCLUSION: We could not confirm recent findings that SGLT2 inhibition reduced glucose absorption and increased osmotic water transport during experimental PD.

Post-kidney donation glomerular filtration rate measurement and estimation.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73m2) and 13.8% (60ml/min/1.73m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

Post-kidney donation glomerular filtration rate measurement and estimation. / Medición y estimación del filtrado glomerular posdonación renal.

BACKGROUND: Long-term consequences associated with kidney donation are controversial. Pre- and post-donation glomerular filtration rates (GFRs) are determinants of renal and cardiovascular risk weighting. In Latin America, there is limited experience in evaluating kidney function using GFR measurement techniques in kidney donors. The MDRD 4-variable and CKD-EPI equations are considered reasonable options. The objective of this study was to evaluate the performance of the MDRD and CKD-EPI equations in post-nephrectomy GFR dynamics in kidney donors. MATERIALS AND METHODS: A prospective cohort study with GFR measurement and estimation in 189 kidney donors who underwent nephrectomy between 2007 and 2016 at the Hospital Privado Universitario de Córdoba [Private University Hospital of Córdoba] in Córdoba, Argentina. GFRs were evaluated before and after nephrectomy by iothalamate clearance determined by HPLC and by the MDRD and CKD-EPI equations for estimating GFR. Two groups were formed for this study: Group 1 (n=107), with an evaluation time subsequent to GFR stabilization (3 months) of up to 5 years, and Group 2 (n=82), with an evaluation time of 5-10 years following donation. Measured GFR (mGFR) was assessed by iothalamate clearance determined by HPLC. RESULTS: Renal compensation values were 61.9% (52.0%-71.1%) and 75.6% (64.9%-84.4%) for Group 1 (n=107) and Group 2 (n=82), respectively. MDRD underestimated the GFR in 3.2% (90ml/min/1.73m2) and 38.6% (60ml/min/1.73m2) compared to the mGFR, and CKD-EPI underestimated the GFR in 2.6% (90ml/min/1.73 m2) and 13.8% (60ml/min/1.73 m2). Diagnostic performance was evaluated with a ROC curve (mGFR<60ml/min/1.73 m2) for MDRD (ABC=0.66; CI: 0.59-0.73; sensitivity: 98.7%; specificity: 63.3%) and for CKD-EPI (ABC=0.79 CI: 0.73-0.85; sensitivity: 96.9%; specificity: 76.4%. Estimated GFR (eGFR) showed poor performance for estimating the glomerular filtration rate in the post-nephrectomy follow-up of donors over 50 years of age. CONCLUSIONS: Equations for estimating GFRs showed poor performance for long-term follow-up of post-nephrectomy GFRs. Measuring GFRs to determine kidney function is recommended in the screening and follow-up of some donors under the current selection criteria.

[ABO incompatible living donor kidney transplantation in a center in Córdoba, Argentina]. / Trasplante renal donante vivo ABO incompatible en un centro de Córdoba, Argentina.

The ABO incompatible (ABOi) living donor (LD) kidney transplant allows increasing the number of donors and reducing the time on the waiting list. The objectives of this study were to compare graft survival, patient survival, rejection risk factors and complications during the first year p ost-transplantation in patients who received an ABOi LD kidney transplant between 2014 and 2019 in our institution, matched according to sex, age and immunological risk with a control group of ABO compatible (ABOc) LD kidney transplants in the same period. Thirteen patients were included in each group. No significant differences were found between ABOi and ABOc in the incidence of delayed graft function (n = 0 vs. 1), bleeding (0 vs. 0), infections (13 vs. 13), cellular rejection (1 vs. 3) and humoral rejection (4 vs. 3) in the first year after transplantation. The rejection rate in ABOi do not seem to be related to blood incompatibility. No risk factors associated with rejection were found. Overall survival of patients was 100% in both groups, and graft survival was 92.3% in ABOi and 100% in ABOc (p = 1). ABOi kidney transplantation is an adequate feasible option in our environment for those who do not have compatible donors.

El trasplante renal con donante vivo (DV) ABO incompatible (ABOi) permite aumentar el número de donantes y reducir el tiempo en lista de espera. Los objetivos de este estudio fueron: comparar la supervivencia del injerto, del paciente, los factores de riesgo de rechazo y las complicaciones durante el primer año post-trasplante en los pacientes que recibieron un trasplante DV ABOi entre 2014 y 2019 en nuestra institución, emparejados según sexo, edad y riesgo inmunológico con un grupo control de trasplantados DV ABO compatibles (ABOc) en el mismo periodo. Se incluyeron 13 pacientes en cada grupo. No se hallaron diferencias significativas entre los ABOi vs ABOc en la incidencia de retardo de la función del injerto (n = 0 vs. 1), sangrado (0 vs. 0), infecciones (13 vs. 13), rechazo celular (1 vs. 3) y rechazo humoral (4 vs. 3) en el primer año posttrasplante. La tasa de rechazo en los pacientes ABOi no parece tener relación con la incompatibilidad sanguínea, ni se hallaron otros factores de riesgo asociados a rechazo. La supervivencia global de los pacientes fue del 100% en ambos grupos, y la del injerto fue del 92.3% en ABOi y 100% en ABOc (p = 1). El trasplante renal ABOi es una adecuada opción factible en nuestro medio para quienes que no cuentan con donantes compatibles.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up.

Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary studies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad cardiovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p < 0.001). El mejor punto de corte fue de 5 (sensibilidad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

ISPD recommendations for the evaluation of peritoneal membrane dysfunction in adults: Classification, measurement, interpretation and rationale for intervention.

GUIDELINE 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point). GUIDELINE 2A: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point). GUIDELINE 2B: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point). GUIDELINE 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is <400 ml (3.86% glucose/4.25% dextrose) or <100 ml (2.27% glucose /2.5% dextrose), (GRADE 1B) and/or (b) the daily UF is insufficient to maintain adequate fluid status. (practice point) Besides membrane dysfunction, low UF capacity can also result from mechanical problems, leaks or increased fluid absorption across the peritoneal membrane not explained by fast PSTR. GUIDELINE 4A: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B). GUIDELINE 4B: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point). GUIDELINE 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and 'lymphatic' reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point). GUIDELINE 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point).

Optimized vs. Standard Automated Peritoneal Dialysis Regimens (OptiStAR): study protocol for a randomized controlled crossover trial.

BACKGROUND: It has been estimated that automated peritoneal dialysis (APD) is currently the fastest growing renal replacement therapy in the world. However, in light of the growing number of diabetic patients on peritoneal dialysis (PD), the unwanted glucose absorption during APD remains problematic. Recent results, using an extended 3-pore model of APD, indicated that large reductions in glucose absorption are possible by using optimized bi-modal treatment regimens, having "UF cycles" using a higher glucose concentration, and "Clearance cycles" using a low concentration or, preferentially, no glucose. The present study is designed to test the theoretical prediction of a lower glucose absorption using these novel regimes. METHODS: This study is a randomized single-center, open-label, prospective study. Prevalent PD patients between 18 and 75 years old without known catheter problems or recent peritonitis are eligible for inclusion. Patients are allocated to a first treatment session of either standard APD (6 × 2 L 1.36% over 9 h) or optimized APD (7 × 2 L 2.27% + 5 × 2 L 0.1% over 8 h). A second treatment session using the other treatment will be performed in a crossover fashion. Samples of the dialysis fluid will be taken before and after the treatment, and the volume of the dialysate before and after the treatment will be carefully assessed. The primary endpoint is difference in glucose absorption between the optimized and standard treatment. Secondary endpoints are ultrafiltration, sodium removal, Kt/V urea, and Kt/V Creatinine. The study will be closed when a total of 20 patients have successfully completed the interventions or terminated according to interim analysis. A Monte Carlo power analysis shows that the study has 80% power to detect a difference of 10 g (in line with that of theoretical results) in glucose absorption between the two treatments in 10 patients. DISCUSSION: The present study is the first clinical investigation of optimized bi-modal treatments proposed by recent theoretical studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04017572. Registration date: July 12, 2019, retrospectively registered.

Policies and health care financing issues for dialysis in Latin America: extracts from the roundtable discussion on the economics of dialysis and chronic kidney disease.

During the 2008 Congress of the International Society for Peritoneal Dialysis, academic nephrologists, nephrology societies, and government officials from Colombia, Brazil, Argentina, Chile, Central America, Ecuador, and Mexico participated in a roundtable discussion on the Economics of Dialysis and Chronic Kidney Disease in Latin America. The main focus was policy and health care financing. The roundtable promoted open discussion between policymakers and clinicians on how to find viable solutions to contain spending on treatment for end-stage renal disease into the future. A number of options were proposed, including early medical intervention (disease management programs) to slow the progression of chronic kidney disease in high-risk patients, promotion of pre-emptive renal transplantation, and use of the most cost-effective dialysis therapy that can be offered to a patient without compromising outcome. It was concluded that the burden of treating more patients in the future could be alleviated by wider utilization of peritoneal dialysis (PD). However, important changes in health care reimbursement systems and realignment of incentives in the region are required to support wider PD penetration.

[Usefulness of equations based on serum cystatin C concentration in the study of renal function]. / Utilidad de las ecuaciones basadas en la concentracion serica de cistatina C en el estudio de la funcion renal.

Serum creatinine is an insensitive marker to identify early changes in glomerular filtration rate (GFR), for this reason alternative methods to estimate renal function result of great clinical importance. Forty-one patients were studied using creatinine clearance modified with cimetidina (Clcrc) as surrogate of GFR, cystatin C-based equations (i.e. Larsson and Hoek formulas), Cockroft-Gault and MDRD abbreviated equations. In the whole group, as well as in those patients with serum creatinine < or =1.2 mg/dl--but reduced renal function: Clcrc 62.01 +/- 17.33 ml/ min/1.73 m(2)-, Larsson and Hoek equations showed higher correlations and lower bias than creatinine-based formulas. Abbreviated MDRD equation showed good performance just in those patients with evident alteration of renal function (serum creatinine > 1.2 mg/dl). We concluded that in patients with different stages of renal function, cystatin C-based equations detect reduction of renal function earlier than the serum creatinine-based formulas.