Use of tocilizumab in kidney transplant recipients with COVID-19.

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.

Peritoneal Dialysis Can Be an Option for Dominant Polycystic Kidney Disease: an Observational Study.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) has been considered a relative contraindication for peritoneal dialysis (PD), although there are few specific studies available. METHODS: A multicenter historical prospective matched-cohort study was conducted to describe the outcome of ADPKD patients who have chosen PD. All ADPKD patients starting PD (n = 106) between January 2003 and December 2010 and a control group (2 consecutive patients without ADPKD) were studied. Mortality, PD-technique failure, peritonitis, abdominal wall leaks and cyst infections were compared. RESULTS: Patients with ADPKD had similar age but less comorbidity at PD inclusion: Charlson comorbidity index (CCI) 4.3 (standard deviation [SD] 1.6) vs 5.3 (SD 2.5) p < 0.001, diabetes mellitus 5.7% vs 29.2%, p < 0.001 and previous cardiovascular events 10.4% vs 27.8%, p < 0.001. No differences were observed in clinical events that required transient transfer to hemodialysis, nor in peritoneal leakage episodes or delivered dialysis dose. The cyst infection rate was low (0.09 episodes per patient-year) and cyst infections were not associated to peritonitis episodes. Overall technique survival was similar in both groups. Permanent transfer to hemodialysis because of surgery or peritoneal leakage was more frequent in ADPKD. More ADPKD patients were included in the transplant waiting list (69.8 vs 58%, p = 0.04) but mean time to transplantation was similar (2.08 [1.69 - 2.47] years). The mortality rate was lower (2.5 vs 7.6 deaths/100 patient-year, p = 0.02) and the median patient survival was longer in ADPKD patients (6.04 [5.39 - 6.69] vs 5.57 [4.95 - 6.18] years, p = 0.024). CONCLUSION: Peritoneal dialysis is a suitable renal replacement therapy option for ADPKD patients.

Evolución natural de la función renal en el anciano: análisis de factores de mal pronóstico asociados a la enfermedad renal crónica / Natural progression of renal function in the elderly: analysis of poor prognosis factors associated with chronic kidney disease

En los últimos años se ha generado un debate sobre el rango de función renal normal y el ritmo de progresión de la enfermedad renal en el anciano. En esta revisión analizamos, basándonos en los resultados del estudio Ancianos con enfermedad renal crónica del Hospital General de Segovia, los factores de mal pronóstico asociados a esta enfermedad: proteinuria, episodios de fracaso renal agudo y de insuficiencia cardíaca, y el papel del ácido úrico. Los ancianos con enfermedad renal crónica que presenten estos factores de mal pronóstico serían los que se podrían beneficiar del seguimiento por Nefrología (AU)

In the last few years a debate has emerged on the range of normal renal function and the rate at which renal disease progresses in the elderly. In this review we analysed, on the basis of the results of the study Ancianos con enfermedad renal crónica del Hospital General de Segovia (Elderly people with chronic kidney disease of the Hospital General de Segovia), the poor prognosis factors associated with this disease: proteinuria, episodes of acute renal failure and heart failure, and the role of uric acid. Elderly people with chronic kidney disease who present these poor prognosis factors may benefit from follow-up by Nephrology (AU)

Natural progression of renal function in the elderly: analysis of poor prognosis factors associated with chronic kidney disease.

In the last few years a debate has emerged on the range of normal renal function and the rate at which renal disease progresses in the elderly. In this review we analysed, on the basis of the results of the study Ancianos con enfermedad renal crónica del Hospital General de Segovia (Elderly people with chronic kidney disease of the Hospital General de Segovia), the poor prognosis factors associated with this disease: proteinuria, episodes of acute renal failure and heart failure, and the role of uric acid. Elderly people with chronic kidney disease who present these poor prognosis factors may benefit from follow-up by Nephrology.

Serum uric acid as a marker of all-cause mortality in an elderly patient cohort.

INTRODUCTION: There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. PATIENTS AND METHODS: Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24-hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. STATISTICAL ANALYSIS: SPSS15.0. RESULTS: baseline SUA was normally distributed and its median was 5.85 mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00 ± 1.74 vs 5.90 ± 1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. CONCLUSIONS: In our study, levels of SUA are an independent risk factor for mortality in elderly patients.

Utilidad del ácido úrico como marcador de mortalidad global en una cohorte de ancianos / Serum uric acid as a marker of all-cause mortality in an elderly patient cohort

Introducción: Existe evidencia creciente del papel del ácido úrico (AU) como factor de riesgo cardiovascular y renal. En este trabajo analizamos la asociación entre niveles basales de AU y mortalidad global en una cohorte de ancianos seguidos prospectivamente durante 5 años. Pacientes y métodos: 80 pacientes clínicamente estables; mediana de edad, 83 años (rango 69-97); 31,3% varones; 35% diabéticos; 83% hipertensos; reclutados aleatoriamente en consultas de Geriatría y Nefrología entre enero y abril de 2006 y seguidos durante 5 años. Medimos basalmente AU y creatinina en plasma y estimamos filtrado glomerular (FG) con fórmula MDRD abreviada. Asimismo, en los pacientes de Nefrología se midió la proteinuria mediante la recogida de orina de 24 horas, y en los vistos en Geriatría se estimó a partir del cociente proteínas (mg/dl)/creatinina (mg/dl) en primera orina de la mañana. Registramos edad, género, comorbilidad basal (Índice de Charlson), patologías cardiovasculares individualizadas, tratamientos y mortalidad. Estadística: SPSS15.0. Resultados: El AU basal presentaba una distribución normal y su mediana era de 5,85 mg/dl. No encontramos diferencias significativas en los niveles de AU según género, antecedentes de diabetes méllitus, hipertensión arterial, uso de diuréticos, cardiopatía isquémica, arteriopatía periférica o ictus. Los pacientes con antecedentes de insuficiencia cardíaca tenían AU significativamente mayor (7,00 ± 1,74 vs. 5,90 ± 1,71; p = 0,031). 41 pacientes (15 varones y 26 mujeres) fallecieron: 15 por deterioro en el estado general; 8 por infecciones; 4 por ictus; 4 por tumores; 3 por causas cardiovasculares; 2 por complicaciones de fracturas y 5 por causas desconocidas. Los pacientes con AU superior a la mediana tenían un FG significativamente menor y una mortalidad a los 5 años más elevada. En el análisis de Cox para mortalidad global (variables independientes: edad, género, Charlson, antecedentes de insuficiencia cardíaca, AU, creatinina, proteinuria y filtrado glomerular-MDRD) sólo los niveles de AU (riesgo relativo: 1,35; 1,17-1,56, p = 0,000) se asociaban de forma independiente a la mortalidad. Conclusiones: en nuestro estudio, los niveles de AU se muestran como factor de riesgo independiente de mortalidad en ancianos (AU)

Introduction: There is growing evidence of the role of serum uric acid (SUA) as a risk factor for cardiovascular and renal disease. We analysed the association between baseline SUA and overall mortality in a cohort of elderly patients followed prospectively for 5 years. Patients and Methods: Eighty clinically stable patients, median age 83 years (range 69-97), 31.3% men, 35% diabetics, 83% hypertensives were randomly recruited at Geriatrics and Nephrology visits between January and April 2006 and followed for 5 years. We measured baseline SUA and serum creatinine and estimated glomerular filtration rate (GFR) with MDRD abbreviated. In Nephrology Department patients, we measured proteinuria in 24-hour urine and in Geriatrics department patients we measured proteinuria (mg/dl)/creatinine (mg/dl) in urine (first morning urine). Predictive variables were: baseline SUA and plasma creatinine; estimated GFR (abbreviated MDRD formula); and we recorded age, gender, baseline comorbidity (Charlson index), individualised cardiovascular treatment and mortality. Statistical analysis: SPSS15.0. Results: baseline SUA was normally distributed and its median was 5.85mg/dl. We found no significant differences in levels of SUA by gender, history of diabetes mellitus, hypertension, diuretic drug use, heart disease, peripheral arterial disease or stroke. Patients with a history of heart failure had significantly higher SUA (7.00±1.74 vs 5.90±1.71, P=.031). Some 41 deaths occurred during follow-up (15 men and 26 women): 15 due to general deterioration, 8 due to infections, 4 due to stroke, 4 due to tumours, 3 due to cardiovascular disease, 2 due to complications of fractures and 5 due to unknown causes. Patients with SUA higher than the median had significantly lower GFR and higher mortality at 5 years. In the Cox analysis for overall mortality [independent variables: age, gender, Charlson Index, history of heart failure, SUA, creatinine, proteinuria and GFR (MDRD)] only SUA levels (HR: 1.35; 1.17-1.56 P=.000) were independently associated with mortality. Conclusions: In our study, levels of SUA are an independent risk factor for mortality in elderly patients (AU)

High stable serum adiponectin levels are associated with a better outcome in prevalent dialysis patients.

AIMS: Our aim was to evaluate the prognostic value of 2 measurements of serum adiponectin levels for all-cause mortality and cardiovascular (CV) mortality in uremic patients. METHODS: We analyzed 184 patients (19-86 years) undergoing peritoneal dialysis (n = 86) or hemodialysis (n = 98). All patients had 2 measurements of serum adiponectin levels (at baseline and after 1 year). Relationships between adiponectin and mortality were studied by means of survival analysis and Cox regression analysis. RESULTS: During a median follow-up time of 31.2 months, 67 patients (36.4%) died, 26 (14.1%) as a result of CV disease. Mean survival time for CV mortality in patients with 1-year adiponectin values in the upper tertile was significantly higher than that found in patients in the middle and lower tertiles. Hazard ratios (HR) for all-cause mortality per SD change were 0.70 (95% CI, 0.50-0.98; p < 0.05) for baseline adiponectin levels and 0.68 (0.49-0.95; p < 0.05) for mean baseline and 1-year adiponectin levels. Mean adiponectin levels were also negatively related with CV mortality [HR 0.43 (0.21-0.86); p < 0.05] and CV events [HR 0.74 (0.55-0.99); p < 0.05]. CONCLUSIONS: In this population of dialysis patients, adiponectin seems to behave as a CV protective factor. Patients with high mean adiponectin levels had a better survival rate.

Nephrotic-range proteinuria in a patient with a giant prolactinoma.

We report for the first time a case of nephrotic-range proteinuria adequately controlled by using dopamine agonists. A 40-year-old man was studied because of persistent asymptomatic nephrotic proteinuria despite lifestyle modifications and treatment with converting enzyme inhibitors. The renal biopsy specimen did not show histopathologic changes. In the follow-up period, a giant prolactinoma was found by chance with extremely high prolactin (PRL) values. After establishing cabergoline therapy, we achieved a remarkable decrease in both serum PRL levels and tumor mass, and surprisingly, proteinuria disappeared. We discuss the possible pathogenic mechanisms of proteinuria that may correspond to PRL level in urine (prolactinuria) or another tumor-related protein.

Serum ghrelin concentrations in patients with chronic renal failure undergoing dialysis.

BACKGROUND: Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated. OBJECTIVE: Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis). PATIENTS AND MEASUREMENTS: We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects. RESULTS: Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found. CONCLUSIONS: These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.

Serum concentrations of leptin, adiponectin and resistin, and their relationship with cardiovascular disease in patients with end-stage renal disease.

BACKGROUND AND OBJECTIVE: High levels of some adipocytokines have been reported in patients with chronic renal failure, but little information is available on adipocytokine concentrations in uraemic patients under different modalities of therapy. Our aims were (1) to quantify the serum concentrations of leptin, adiponectin and resistin in uraemic patients on peritoneal dialysis (PD) and haemodialysis (HD), in comparison with patients on conservative management, and (2) to study the relationships between adipocytokine levels and previous atherosclerotic vascular disease. PATIENTS AND MEASUREMENTS: We studied 82 dialysis patients treated by PD (n = 44, 23 males and 21 females, mean age 54.4 +/- 1.8 years) or HD (n = 38, 22 males and 16 females, age 60.8 +/- 1.6 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of leptin, adiponectin and resistin were measured in all subjects. Information on vascular disease (cerebral vascular, peripheral vascular and heart disease) was obtained from a detailed medical history. RESULTS: PD patients showed significantly higher serum leptin concentrations [median (interquartile range), 28.7 (13.0-71.9) microg/l] than those found in patients on HD [9.7 (4.7-31.9) microg/l, P < 0.01] or in conservative management [5.9 (4.3-38.6) microg/l, P < 0.05]. Adiponectin concentrations were similar in the three groups of patients (mean +/- SEM, 48.0 +/- 4.5 mg/l in PD, 57.7 +/- 4.4 mg/l in HD, and 44.4 +/- 7.0 mg/l in controls, NS). Patients treated by both PD and HD exhibited resistin concentrations significantly higher than those found in controls (26.3 +/- 0.99 and 27.5 +/- 1.4 microg/l, respectively, vs. 17.3 +/- 1.0 microg/l, P < 0.001). Leptin concentrations were positively correlated with body mass index (BMI) (r = 0.287, P < 0.01) and adiponectin levels were negatively related to BMI (r = -0.416, P < 0.001) and the homeostatic model assessment (HOMA-R) index (r =-0.216, P < 0.05). Leptin, adiponectin and resistin levels in patients with previous vascular events were similar to those found in patients without these complications. Logistic regression analysis did not demonstrate any relationship between serum adipocytokine concentrations and the presence of vascular disease of any type. A significant relationship between resistin and heart disease [odds ratio (OR) 1.80 (1.03-3.15), P = 0.039] was found when analysing subgroups of patients. CONCLUSIONS: These data suggest that leptin levels are higher in PD patients, and resistin levels are higher in PD and HD patients in relation to patients on conservative management, whereas adiponectin concentrations are similar in the three groups. These results do not support the presence of a clinically relevant relationship between adipocytokines and previous episodes of vascular disease in the whole population or in patients classified in subgroups, with the only exception of a relationship between resistin levels and heart disease.

Growth hormone, IGF-I and its binding proteins (IGFBP-1 and -3) in adult uraemic patients undergoing peritoneal dialysis and haemodialysis.

OBJECTIVE: The GH/IGF axis is altered in chronic renal failure (CRF). CRF patients usually show normal or high serum concentrations of GH and IGF-I, whereas all IGF binding proteins (IGFBP-1 to -6), except IGFBP-5, considerably increase with declining renal function. The aims of the present study were to quantify serum concentrations of GH, IGF-I, IGFBP-1 and IGFBP-3 in a group of patients with CRF, and determine whether there were differences according to the type of dialysis, that is, peritoneal dialysis (PD) and haemodialysis (HD). DESIGN: A cross-sectional study in the setting of a dialysis unit of a general hospital. PATIENTS AND MEASUREMENTS: We studied 108 dialysis patients treated by PD (n = 54, 32 males and 22 females, mean age 61.0 +/- 1.4 years) or HD (n = 54, 31 males and 23 females, age 62.6 +/- 1.5 years). A group of 42 healthy subjects of similar age, sex and body mass index (BMI) served as the control group. Baseline serum concentrations of GH, insulin, IGF-I, IGFBP-1 and IGFBP-3 were measured in all patients and control subjects. RESULTS: Fasting serum concentrations of IGF-I and its binding proteins (IGFBP-1 and IGFBP-3) were significantly higher in dialysis patients than in subjects with normal renal function. IGF-I (248.9 +/- 23.4 vs. 205.5 +/- 15.5 micro g/l, NS), IGFBP-3 (5.6 +/- 0.4 vs. 5.5 +/- 0.2 mg/l, NS) and IGFBP-1 (36.1 +/- 5.9 vs. 44.1 +/- 6.5 micro g/l, NS) concentrations were similar in both groups of dialysis (PD vs. HD) patients. However, GH (2.3 +/- 0.3 vs. 1.1 +/- 0.1 micro g/l, P < 0.001) and insulin (40.4 +/- 4.5 vs. 30.1 +/- 3.1 micro U/ml, P < 0.05) levels were significantly higher in the PD group than in the HD group. Both groups of dialysis patients showed significantly higher levels of insulin than healthy subjects (14.7 +/- 1.9 micro U/ml, P < 0.0001 and P < 0.01 for PD and HD, respectively). In both groups of dialysis patients, IGF-I correlated inversely with IGFBP-1 (PD group r = -0.46, P = 0.0006; HD group r = -0.57, P = 0.0001) and directly with IGFBP-3 (PD group r = 0.44, P = 0.001; HD group r = 0.73, P = 0.001). No correlation between insulin and IGFBP-1 was found in any of the groups studied. CONCLUSIONS: These findings demonstrate that adult dialysis patients have elevated IGF-I, IGFBP-1 and IGFBP-3 serum concentrations compared with subjects with normal renal function. Only GH and insulin show statistically significant differences in relation to type of dialysis. Finally, the negative correlation between IGF-I and IGFBP-1 and the positive correlation between IGF-I and IGFBP-3 are maintained in both groups of adult dialysis patients.

Obstructive ARF caused by an inflammatory abdominal aortic aneurysm.

Inflammatory abdominal aortic aneurysms are rare entities characterized by dense fibrosis typically enveloping the aortic wall and adjacent structures with distinctive clinical features that differentiate them from typical atherosclerotic aneurysms. The inflammatory process can involve the renal excretory pathways, causing ureteral obstruction in 20% of cases. The authors report 2 cases of complete obstructive anuria secondary to inflammatory aneurysms and discuss the most appropriate management for these situations of hydronephrosis. Surgical repair of the aneurysm usually leads to regression of the inflammatory reaction.