Prevalence of factors related to vascular calcifications in patients with chronic kidney disease on dialysis.

The main aim of the study was to determine the prevalence of vascular calcifications in patients with chronic kidney disease on dialysis in our population assessed by X-ray. The secondary objectives were to determine the cardiovascular risk factors associated with the presence of vascular calcifications and to evaluate the complementary use of the echocardiogram in a cross-sectional, observational, multicentric study. We included patients with chronic kidney disease on dialysis, age =18 years with at least 3 months of renal replacement therapy in 8 dialysis centres in Argentina. The degree of vascular calcification was determined using Adragao and Kauppila scores. The presence of valvular calcifications was established through a trans-thoracic doppler echocardiogram. Univariate and multivariate analysis were undertaken, considering the degree of vascular calcification as the dependent variable; 443 adult patients were evaluated at 8 centres across 5 provinces in Argentina. The prevalence of vascular calcifications by the X-rays was 63%, while 73% presented calcifications in hands and pelvis, with an Adragao score > 3, and 60% presented calcifications in the abdominal aorta with a Kauppila score > 4. The prevalence of valvular calcifications: 28%. We have shown a higher rate of vascular calcifications with the use of plain X-rays when compared to the prevalence of valvular calcifications obtained with echocardiograms. In this regard, valvular calcifications were present particularly in those patients with a severe level of radiological vascular calcification.

[Kidney involvement in Idiopathic Light Chain disease. Report of one case]. / Enfermedad renal por depósito idiopático de cadenas livianas: Caso clínico.

Idiopathic Light Chain disease (ILCD) is a systemic disease characterized by a deposit in different organs of light chain monoclonal immunoglobulins, produced by an abnormal clone of B cells. It is usually found in the course ofa plasma cell dyscrasia and in other lymphoproliferative alterations; however it may occur in absence of any hematologic disease and is denominated as idiopathic. We report a 51-year-old mole admitted to the hospital due to anasarca. Laboratory evaluation showed a serum creatinine of 1.4 mg/dl, a serum albumin of1.6 g/dl, a serum cholesterol of 687 mg/dl and a proteinuria of 5.3 g/day Light chains with a predominance of a monoclonal component were identified in urinary proteins by electrophoresis and kappa chains were identified by immunofixation. A renal biopsy showed a diffuse nodular glomerulopathy with a 35% tubular atrophy and interstitial sclerosis. Electrón microscopy confirmed light chain deposition. The bone marrow biopsy showed a myeloid hyperplasia. The patient was initially treated with methylprednisolone and plasmapheresis with a reduction in serum creatinine and disappearance of urinary kappa component. Albuminuria persisted and a malnutrition-inflammatory complex syndrome was diagnosed. Hemodialysis with ultrafiltration was started along with cyclophosphamide. The patient received hemodialysis for six months and continued with methylprednisolone.

Pro-calcitonin and inflammation in chronic hemodialysis.

UNLABELLED: Procalcitonin (PCT) has emerged as a marker of infection, a frequent complication in hemodialysis (HD). We analyzed PCT levels in chronic non-acutely infected HD subjects, assessed its correlation with inflammatory and nutritional markers and propose a PCT reference value for non-infected HD patients. In an observational cross-sectional study, 48 chronic HD patients and 36 controls were analyzed. VARIABLES: age, gender, time on HD; diabetes; vascular access, PCT, C-reactive protein (CRP), albumin, malnutrition inflammatory score (MIS), hematocrit, leukocyte count, and body mass index (BMI). Subsequently, control (G1, n = 36, 43%) vs. non-infected patients (G2, n = 48, 57%) groups were compared. In control subjects (G1), age: 54.3 ± 13.7 years, range (r): 30-81; males: 19 (53%); median PCT 0.034 ng/ml (r: 0.02-0.08); median CRP 0.80 mg/ dl (r: 0.36-3.9); p95 PCT level: 0.063 ng/ml. In G2, age: 60.2 ± 15.2 years; males 32 (67%), time on HD: 27.0 ± 24.4; diabetics: 19 (32%); median PCT: 0.26 ng/ml (r: 0.09-0.82); CRP: 1.1 mg/dl (r: 0.5-6.2); p95 PCT level: 0.8 ng/ml. In control subjects, PCT and CRP were significantly lower than in G2: PCT: 0.034 vs. 0.26 ng/ml, p = 0.0001; CRP: 0.8 vs. 1.1 mg/dl, p = 0.0004. PCT-CRP correlation in G2: p = 0.287, p = 0.048. PCT and CRP concentrations are elevated in chronic non-acutely infected HD subjects, independently of infection, diabetes and vascular access. A p95 PCT level of 0.8 ng/ml may be considered as the upper normal reference value in non-acutely infected HD subjects. The PCT cut-off level in HD is yet to be determined in HD.

[Guidelines for diagnosis, monitoring and treatment of Fabry disease]. / Guía para el diagnóstico, seguimiento y tratamiento de la enfermedad de Fabry.

Fabry disease is an X-linked hereditary lysosomal storage disorder caused by deficiency of the enzyme alpha-galactosidase A. Knowledge about this disease, and its medical management, has made remarkable progress in the last decade, including the development of its specific treatment. This guide was developed by medical professionals from various specialties involved in the care of patients with Fabry disease. The discussion and analysis of the available scientific evidence, coupled with the experience of each of the participants, has allowed us to develop the concepts included in this guide in order to provide a useful tool for all professionals who care for patients with Fabry disease.

Metabolic diagnosis in stone formers in relation to body mass index.

It is known that several metabolic abnormalities that favor stone formation have a strong dependence on environmental and nutritional factors. The incidence and prevalence of kidney stone is increasing while there has been a parallel growth in the overweight/obesity rate, and epidemiologic studies have shown a significant association between overweight/obesity and increased nephrolithiasis risk. The aim of this study was to assess if metabolic abnormalities observed in stone patients differ in relation to their BMI. We evaluated 817 renal stone formers (459 men and 358 woman) in an outpatient setting. They were all studied with a standard protocol (two 24 h urine collections and serum parameters) and classified according to their BMI in normal, overweight and obese and according to age in <50 or >50 year old. In the whole population we found that 58.7% were either overweight or obese: 39.4% (n = 322) were OW and 19.3% (n = 158) were OB. The proportion of overweight was significantly higher among men than women. In women of all ages regardless of BMI, hypercalciuria was the most prevalent diagnosis. Hyperuricosuria increased its prevalence significantly only in overweight and obese women <50 years of age (p < 0.01). Hypercalciuria was the predominant diagnosis in normal weight men of both age groups. Hyperuricosuria was the most frequent abnormality in overweight and obese men followed by gouty diathesis and both increased their prevalence significantly from normal weight to obesity and in both age groups (p < 0.05 and <0.01). We conclude that the only abnormalities that increased their prevalence significantly with increasing BMI were hyperuricosuria and gouty diathesis, the first one in men of all ages and women under 50 years of age, while the second one only in men.

Central Venous Reflux, a Rare Cause of Neurological Manifestations in Hemodialysis Patients: A Case Report and Literature Review.

Central venous disease (CVD) is a serious complication in hemodialysis patients. Neurological manifestations are rare. We describe a female with end-stage renal disease with throbbing headache accompanied by paresthesia, weakness, and abnormal posture of her right hand during dialysis sessions. Motor symptoms completely resolved after each dialysis session, although the headaches persisted for several hours. No neurological deficit was evidenced on physical examination. Digital subtraction angiography identified an incomplete thrombosis of the left brachiocephalic vein with retrograde flow in the internal jugular vein, sigmoid sinus, and transverse sinus on the left side. This case illustrates that cerebral venous congestion due to CVD can produce neurological symptoms. Furthermore, we systematically review the literature to identify the characteristics of the cases described so far. This allows clinicians to know the entity and have a high index of suspicion in a hemodialysis patient who develops neurological symptoms.

Elevated pro-brain natriuretic peptide, troponin T and malnutrition inflammatory score in chronic hemodialysis patients with overt cardiovascular disease.

BACKGROUND: We assessed the relationship between pro-brain natriuretic peptide (pro-BNP), troponin T (TropT) and nutritional status. METHODS: A total of 48 chronic hemodialysis patients were grouped according to the presence [group A (GA); n = 24] or not [group B (GB)] of cardiovascular disease. RESULTS: Compared to GB subjects, GA subjects were older, had been on hemodialysis for a longer period and had higher prevalences of vascular grafts, hypertension and elevated C-reactive protein (CRP) [GA vs. GB: 1.1 (range 0.1-32.9) vs. 0.4 (0-28.1) mg/dl; p = 0.028], malnutrition inflammatory score (MIS) (GA vs. GB: 7.50 vs. 4.00; p = 0.001), pro-BNP [GA vs. GB: 6,760 (601-103,200) vs. 686 (75-83,700) pg/ml; p < 0.001] and TropT [GA vs. GB: 0.3650 (0.011-0.199) vs. 0.010 (0.0-0.290) ng/ml; p = 0.002]. Pro-BNP correlated with TropT (rho 0.539; p < 0.001), MIS (rho 0.502; p < 0.0001), homocysteine (rho 0.321; p = 0.13) and CRP (rho 0.511; p < 0.0001). Pro-BNP levels were lower in GB patients as the body mass index increased; the opposite occurred in GA. CONCLUSIONS: Patients with cardiovascular disease had elevated pro-BNP and TropT levels. In patients without cardiovascular disease, malnutrition and inflammation were associated with vascular prostheses, while pro-BNP was lower in obese patients.

["Malnutrition-inflammation complex syndrome" in chronic hemodialysis]. / "Sindrome complejo de malnutricion e inflamacion" en la hemodialisis cronica.

Protein-energy wasting (PEW) and inflammation are usually common and concurrent conditions in maintenance dialysis patients and associated with poor prognosis. Low appetite and hypercatabolic states are common features. In dialysis patients, the former has been suggested to be secondary to inflammation; however, the evidence is not conclusive. Hence, the term malnutrition-inflammation complex syndrome (MICS) was coined to include this clinical entity, regardless the original causes. Possible causes of MICS include comorbid illnesses, oxidative stress, nutrient loss through dialysis, hyporexia, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, increased blood phosphate and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hypo-responsiveness, cardiovascular atherosclerotic disease, decreased quality of life, hospitalization and increased mortality in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, decrease in muscle mass, hypocreatininemia and hypohomocysteinemia, a "reverse epidemiology" phenomenon of cardiovascular risk factors can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine, within certain limits, appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed in this paper. The correct management of MICS may diminish the cardiovascular disease, main cause of death in this population.

H1N1 infection and the kidney in critically ill patients.

BACKGROUND: Acute renal failure due to viral infections is rare. We assessed the development of acute kidney injury (AKI) in critically compromised patients due to the H1N1 influenza virus. METHODS: All patients with a PCR -confirmed diagnosis of H1N1 influenza infection admitted to the intensive care unit between May and July 2009 were retrospectively studied. Thereafter, the risk factors associated with the development of acute renal injury, the requirements of acute hemodialysis (HD) and death were analyzed. RESULTS: Twenty-two patients with H1N1 pneumonia were included: age: 52.91 ± 18.89 years; gender: males 11 (50%); chronic airway disease: 9 (41%); oncohematological disease: 8 (36.7%); cardiovascular disease 5 (22.7%); chronic renal insufficiency: 4 (18.2%); obesity 3 (13.6%); concomitant pregnancy: 2 (9.1%); diabetes mellitus: 2 (9.1%); previous influenza A vaccination: 9 (41%). All patients received oseltamivir within 48 hours of presumed diagnosis. Seventeen patients (77.3%) developed fever initially. Six patients (27.3%) required noninvasive ventilation assistance and 15 patients (68.2%) received invasive ventilatory support. Mean days on mechanical respiratory assistance: 11 ± 10.35. Arterial partial pressure of oxygen/fraction of inspired oxygen ratio: 140.11 ± 83.03 mmHg. Inotropic drugs were administered to 15 patients (68.2%). Fourteen patients (63.6%) developed AKI. Mean highest creatinine levels: 2.74 ± 2.83 mg/dl. Four patients (18.2%) needed renal replacement therapy with a mean duration of 15 ± 12 days. Six patients (42.9%) recovered renal function. AKI was associated with pregnancy, immunosuppression, high APAC HE, SOFA and MURRA Y scores, and less time on mechanical ventilation assistance, hemodynamical instability and thrombocytopenia. HD requirements were associated with elevated SOFA scores (12.25 ± 1.75 vs. 6.22 ± 0.8, p<0.05), elevated creatine phosphokinase (933 ± 436.6 vs. 189.9 ± 79.3 U/L, p<0.05) and alanine transferase levels (843.3 ± 778.8 vs. 85.33 ± 17.4 U/L, p<0.05). Twelve patients died (54.6%), 10 of whom had acute renal failure (83.3%) and 3 had been on acute HD (25%). Mortality was associated with higher APACHE, SOFA and Murray scores, a higher oseltamivir dose (253.1 ± 25.8 vs. 183.8 ± 27.6 mg, p<0.05), lower oxygen inspired fraction/alveolar pressure ratio (99.3 ± 12.2 vs. 196.3 ± 33.9 mmHg, p<0.01), thrombocytopenia (88966 ± 22977 vs. 141200 ± 17282 mm3, p<0.05), hypoalbuminemia (1.82 ± 0.1 vs. 2.61 ± 0.2 g/dl, p<0.01), acute renal failure (10 vs. 4, p<0.05), oligoanuria (5 vs. 0, p<0.05) and lack of recovery of renal function (2 vs. 4, p<0.01). Three out of 4 (75%) of the hemodialyzed patients died. CONCLUSIONS: In the critically ill due to H1N1 pneumonia, renal insufficiency was a frequent complication, demanding renal replacement therapy in 18% of cases. The need for HD was associated with an elevated risk of death. Mortality was mainly associated with multiple organ failure, oligoanuria, acute renal injury and a lack of recovery of renal function.

[Acute kidney injury in severe sepsis]. / Injuria renal aguda en la sepsis grave.

Sepsis affects 40% of critically ill patients, with a reported mortality of approximately 30% in severe sepsis, raising to 75% when acute kidney injury ensues, which occurs in about 20-51% of cases. The present study consists on a one-year prospective, observational, longitudinal trial undergone in 80 severe septic patients to determine the risk of development of acute kidney injury and its relationship with mortality; the association of the clinical course and blood parameter variations with mortality; the severe sepsis mortality rate; an eventual correlation between death and septic focus, and to assess mortality predictibility based on initial creatinine levels and final variations. Two groups were defined: Dead (n=25) and Not-dead (n=55). According to creatinine on admission, 39 subjects presented with normal creatinine levels (10 deaths) and 41 presented elevated creatinine measurements (15 deaths); regarding final creatinine levels, 48 presented normal levels and 7 patients died, while 32 developed acute kidney injury, with 18 deaths. Of the total of 25 deaths, 72% presented renal injury. Seven alive patients and 2 deceased patients required hemodialysis. The most frequent primary septic focus was the airway (26.4%). The development of kidney injury is a high predictor of mortality in sepsis, independent of initial serum creatinine levels. Older patients, hypertension, a higher APACHE score, a more severe degree of anemia, hypoalbuminemia, hyperphosphatemia and hyperkalemia were associated with a higher mortality rate. The global mortality was: 31.3%. The failure to identify the primary septic focus was associated with higher mortality. The respiratory focus was related with a higher risk to require hemodialysis.

Early decrease in the podocalyxin to synaptopodin ratio in urinary Fabry podocytes.

BACKGROUND: In Fabry nephropathy, podocyturia is an early event that may lead to glomerulosclerosis and chronic kidney disease. The glycocalyx is a potential podocyte damaged compartment in glomerulopathies. We investigated glycocalyx podocalyxin in urinary detached podocytes compared with cytoplasmic synaptopodin. METHODS: This was a cross-sectional study including 68 individuals: Controls (n = 20) and Fabry patients (n = 48), 15 untreated and 33 treated. Variables included age, gender, urinary protein/creatinine ratio (UPCR), estimated glomerular filtration rate (eGFR), lyso-triasocylsphingosine (lyso-Gb3) levels and enzyme replacement therapy (ERT). Podocyturia was assessed by immunofluorescence and podocyte subpopulations were analyzed. RESULTS: Fabry patients displayed higher podocyturia than controls. Fabry treated subjects (n = 33) presented significantly higher UPCR compared with untreated ones (n = 15); podocyturia, eGFR and lyso-Gb3 levels were not different. All control podocytes colocalized synaptopodin and podocalyxin; 13 Fabry patients (27%) colocalized these proteins, while 35 (73%) were only synaptopodin positive. No podocalyxin-positive/synaptopodin-negative cells were encountered. In Fabry patients, podocyturia was significantly higher and proteinuria lower in those that colocalized. CONCLUSION: Fabry patients present higher podocyturia and a presumably more damaged glycocalyx assessed by podocalyxin. Treated patients had significant higher proteinuria suggesting ERT is initiated late, at advanced stages. The degree of podocalyxin-negative podocytes was similar in both groups, but colocalization was associated with lower proteinuria. Podocyturia assessed by podocalyxin alone may be underestimated. The implications of podocyte glycocalyx damage deserve further investigations.

Dual renin-angiotensin system blockade plus oral methylprednisone for the treatment of proteinuria in IgA nephropathy.

Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 +/- 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 +/- 1.86 g/day; serum creatinine 1.07 +/- 0.29 mg/dl; mean follow-up 60.10 +/- 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual renin-angiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 +/- 0.07 g/day (P < 0.001) while serum creatinine did not vary: 1.07 +/- 0.28 mg/dl (P = ns). After a mean follow-up of 42.36 +/- 21.56 months urinary protein excretion (0.12 +/- 0.06 g/day) and renal function (serum creatinine 1.06 +/- 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to < 0.5 g/day in patients with IgA nephropathy without changes in renal function.

In IgA Nephropathy, Glomerulosclerosis Is Associated with Increased Urinary CD80 Excretion and Urokinase-Type Plasminogen Activator Receptor-Positive Podocyturia.

BACKGROUND: Podocyturia may determine the evolution to podocytopenia, glomerulosclerosis, and renal failure. According to the Oxford classification of IgA nephropathy (IgAN), the S1 lesion describes glomerulosclerosis. Urokinase-type plasminogen activator receptor (uPAR) participates in podocyte attachment, while CD80 increases in glomerulosclerosis. We measured uPAR-positive urinary podocytes and urinary CD80 (uCD80) in controls and in IgAN subjects with M1E0S0T0 and M1E0S1T0 Oxford scores to assess a potential association between podocyturia, inflammation, and glomerulosclerosis. METHODS: The groups were as follows: controls (G1), n = 20 and IgAN group (G2), n = 39, subdivided into M1E0S0T0 (G2A), n = 21 and M1E0S1T0 (G2B), n = 18. Among the included variables, we determined uPAR-positive podocytes/gram of urinary creatinine (gUrCr) and uCD80 ng/gUrCr. Biopsies with interstitial fibrosis and tubular atrophy <10% were included. RESULTS: Groups were not different in age and gender; urinary protein-creatinine (uP/C) ratio, Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, uPAR-positive podocytes/gUrCr, and uCD80 were significantly increased in G2 versus G1. G2A and G2B were not different in age, gender, hypertension, and follow-up. G2B displayed significantly higher uP/C, uPAR-positive podocytes, uCD80, and lower CKD-EPI versus G2A. Strong significant correlations were encountered between uCD80 and podocyturia in G2A and G2B. However, when G1 was compared to G2A and G2B separately, the differences with respect to uP/C, uPAR-positive podocytes, and podocyturia were significantly stronger versus G2B than versus G2A. CONCLUSIONS: IgAN presents elevated uCD80 excretion and uPAR-positive podocyturia, while CD80 correlates with podocyturia. Glomerulosclerosis (S1) at the time of biopsy is associated with higher uP/C, lower renal function, increased uPAR-positive podocyturia, and CD80 excretion, and is independent of M1. In IgAN, uPAR may participate in podocyte detachment.

Expression of uPAR in Urinary Podocytes of Patients with Fabry Disease.

Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-ß (n = 21). Variables. Variables are estimated glomerular filtration rate (eGFR), urinary protein : creatinine ratio, and urinary uPAR+ podocyte : creatinine ratio. uPAR mRNA expression in response to lyso-Gb3, a bioactive glycolipid accumulated in Fabry disease, was studied in cultured human podocytes. Results. Controls and Fabry patients had similar age, gender, and renal function. Urinary uPAR+ podocytes were higher in patients than in controls. Untreated patients were significantly younger; had more females, and presented lower urinary protein : creatinine ratios and significantly higher urinary uPAR+ podocytes than treated subjects. In treated patients, urinary uPAR+ podocytes correlated with urinary protein : creatinine ratio (ρ = 0.5; p = 0.02). Lyso-Gb3 at concentrations found in the circulation of Fabry patients increased uPAR expression in cultured podocytes. Conclusions. Urinary podocytes expressing uPAR are increased in Fabry patients, especially in untreated patients. The potential contribution of uPAR expression to podocyte detachment merits further studies.

Clopidogrel diminishes hemodialysis access graft thrombosis.

BACKGROUND: The most common complication of hemodialysis (HD) access graft is thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to prevent this serious complication. METHODS: A prospective study in which 24 patients on chronic HD whose vascular accesses were grafts were divided into two groups: group A (n = 12, 50%) consisted of patients who did not receive antithrombotic therapy after graft creation, and group B (n = 12, 50%) received clopidogrel 75 mg/day from 2 days after surgery onwards. Both groups were not different according to age, gender, cause of renal failure, hematocrit levels, platelet counts and Kt/V. All patients' thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed. Finally, the patient survival difference between both groups was determined. RESULTS: Eleven thrombotic episodes were diagnosed in group A while one event was reported in group B (p < 0.001). Graft access days of patency were significantly longer in group B compared to group A (380.8 +/- 170 vs. 90.1 +/- 57.2, p < 0.001). Time that elapsed from dialysis initiation to graft creation was not different (group A 18 +/- 12 days, group B 20 +/- 10 days). Days on HD were different between both groups (group A 208.9 +/- 97.2 vs. group B 583.2 +/- 287.0, p < 0.001) and all patients from group A (n = 12, 100%) and 2 patients from group B (16.7%) died (p = 0.001). Major bleeding events were not reported. CONCLUSIONS: Clopidogrel significantly decreased thrombotic graft episodes. Patients on clopidogrel had a prolonged vascular access patency, longer time on HD and better survival.

Belatacept and mediastinal histoplasmosis in a kidney transplant patient.

BACKGROUND: In transplantation immunosuppression enhances the appearance of opportunist infections. An ideal balance between the prevention of rejection, the lowest risk of infections and the highest rates of graft survival is a continuous challenge. Lower doses of immunosuppression may diminish the risk of infections, metabolic and hemodynamic complications or even of malignancy, but may expose patients to episodes of acute rejection. New drugs are being developed to improve graft survival at the lowest risk of side effects. Belatacept has recently been introduced in kidney transplantation to inhibit the co-ligand signal of T cell stimulation. It is a drug with a safe profile, is well-tolerated and appears to improve long-term survival of kidney grafts. However, there may be an increase in opportunistic infections which may be facilitated by T cell depression, as Aspergillus sp., Cryptococcus neoformans or tuberculosis. CASE PRESENTATION: We describe a 59-year-old female who developed fever, clinical wasting and a mediastinal mass 31 months after receiving a living non-related kidney transplant while on belatacept therapy. A mediastinal node biopsy disclosed the presence of Histoplasma capsulatum. Infection successfully resolved after appropriate antifungal treatment. CONCLUSIONS: To our knowledge, this is the first reported case of Histoplasma capsulatum in a kidney transplanted patient on belatacept therapy.

Podocyturia is significantly elevated in untreated vs treated Fabry adult patients.

BACKGROUND: Proteinuria suggests kidney involvement in Fabry disease. We assessed podocyturia, an early biomarker, in controls and patients with and without enzyme therapy, correlating podocyturia with proteinuria and renal function. METHODS: Cross-sectional study (n = 67): controls (Group 1, n = 30) vs. Fabry disease (Group 2, n = 37) subdivided into untreated (2A, n = 19) and treated (2B, n = 18). Variables evaluated: age, gender, creatinine, CKD-EPI, proteinuria, podocyte count/10 20× microscopy power fields, podocytes/100 ml urine, podocytes/g creatininuria (results expressed as median and range). RESULTS: Group 1 vs. 2 did not differ concerning age, gender and CKD-EPI, but differed regarding proteinuria and podocyturia. Group 2A vs. 2B: age: 29 (18-74) vs. 43 (18-65) years (p = ns); gender: males n = 3 (16 %) vs. n = 9 (50 %). Proteinuria was significantly higher in Fabry treated patients, while CKD-EPI and podocyturia were significantly elevated in untreated individuals. Significant correlations: group 2A: age-proteinuria, ρ = 0.62 (p = 0.0044); age-CKD-EPI, ρ = -0.84 (p < 0.0001); podocyturia-podocytes/100 ml urine, ρ = 0.99 (p = 0.0001); podocyturia-podocytes/g creatininuria ρ = 0.86 (p = 0.0003), podocytes/100 ml urine-podocytes/g urinary creatinine, ρ = 0.84 (p = 0.0004); proteinuria-CKD-EPI, ρ = -0.68 (p = 0.0013). Group 2B: podocyturia-podocytes/100 ml urine, ρ = 0.88 (p < 0.0001); podocyturia-podocytes/g creatininuria, ρ = 0.84 (p < 0.0001); podocytes/100 ml urine-podocytes/g creatininuria, ρ = 0.94 (p < 0.0001); CKD-EPI-proteinuria, ρ = -0.66 (p = 0.0028). CONCLUSIONS: Patients with Fabry disease display heavy podocyturia; those untreated present significantly higher podocyturia, lower proteinuria and better renal function than those who are treated, suggesting that therapy may be started at advanced stages. Podocyturia may antedate proteinuria, and enzyme therapy may protect against podocyte loss.

[Hyperhomocysteinemia as a vascular risk factor in chronic hemodialysis patients]. / La hiperhomocisteinemia como factor de riesgo vascular en hemodializados crónicos.

Homocysteine is an independent risk factor for cardiovascular disease in the general population. In addition, it plays a main role in the development of atherogenesis and thrombosis, particularly in end-stage renal disease patients. Therefore, hemodialysis patients are under the burden of homocysteine toxic effects, present in nearly 90% of dialysis patients. Our group found that folic acid is an efficient therapeutic approach to decrease homocysteine levels, and the addition of intravenous methylcobalamin potentiates this effect; however, methylcobalamin alone was unsuccessful to normalize homocysteine levels. With time a group of patients required a higher dose of folic acid to reduce hyperhomocysteinemia. Patients homozygous and, to a lesser extent heterozygous, to the C677T thermolabile variant of methylenetetrahydrofolate reductase (MTHFR) presented a reduced catalytic activity and required a higher folic acid dose. Vascular-access thrombotic events were similar in all patients according to the variants of the enzyme, suggesting that treating hyperhomocysteinemia was the key to lower the risk of thromboses. Noteworthy, hypohomocysteinemia, generally acompanying malnourishment, is associated to higher mortality. Albeit hyper-homocysteinemia is considered a vascular risk factor in renal failure patients, it has not yet been established in this population if its correction is associated with a decrease in the rate of vascular disease and thrombosis. However, given the mentioned evidence about the low risk and good tolerance of vitamin therapy, we believe it useful to know folate, cobalamin and homocysteine blood levels in chronic renal patients and start a prompt treatment, which may proof adequate to maintain homocysteine levels of 10 +/- 5 micromol/l.

Metabolismo óseo-mineral en 4620 pacientes prevalentes en hemodiálisis crónica en argentina / Bone-mineral metabolism in 4,620 prevalent patients in chronic hemodialysis in argentina

RESUMEN Introducción: Las anormalidades del metabolismo óseo-mineral comienzan desde las primeras etapas de la enfermedad renal crónica, produciendo el desarrollo de enfermedad ósea y el aumento de la morbimortalidad de los pacientes. Objetivos: Conocer en una muestra representativa de nuestra población en hemodiálisis, la prevalencia de pacientes en rango objetivo de valores de parathormona, hiperparatiroidismo secundario y enfermedad ósea adinámica, de acuerdo con las guías KDIGO, evaluando, además, el uso de diferentes medicamentos en el control de estas alteraciones. Material y métodos: Participaron 39 centros de hemodiálisis de nuestro país, quienes enviaron las últimas determinaciones de calcio, fósforo y parathormona, y la medicación recibida en el manejo del metabolismo mineral. Resultados: Se incluyeron 4620 pacientes prevalentes en hemodiálisis, > 18 años, edad media 57 años, hombres 57,4%. Las medias fueron: calcemia 8,6 y fosfatemia 4,9 mg/dl. De esta población, el 56,7% y el 50,3% estaban en rango de calcemia y fosfatemia, respectivamente. La parathormona promedio fue 601 y la mediana 437 pg/ml. El 50,5% tenía parathormona en rango, el 15% por debajo de 150 y el 34,5% por encima de 600 pg/ml. En relación a la medicación, el 47% de la población recibió quelantes cálcicos, con extremos en su uso, que van desde el 4,5% al 8% en algunos centros, y del 83% al 94% en otros. El 28,8% recibió Sevelamer, calcitriol el 38%, paricalcitol el 11% y cinacalcet el 20%, siendo su uso variable según los centros del 3% al 52%. Conclusiones: La presencia de hiperparatiroidismo secundario es más frecuente que la deseada, probablemente vinculado a la dificultad en el uso adecuado de medicamentos.

ABSTRACT Introduction : Abnormalities of bone mineral metabolism begin from the early stages of CKD, causing the development of bone disease and increased morbidity and mortality of patients. Objectives: To know, in a representative sample of our hemodialysis patients, the prevalence of patients in the target range of PTH values, secondary hyperparathyroidism and adynamic bone disease according to the KDIGO guidelines, also evaluating the use of different drugs in the control of these alterations. Methods: 39 hemodialysis centers from our country participated, who sent the latest determinations of calcium, phosphorus and PTH and the medication received in the management of mineral metabolism. Results: 4620 prevalent hemodialysis patients > 18 years were included, mean age 57 years, men 57.4%. The means were calcemia 8.6 and phosphatemia 4.9 mg/dl. 56.7% and 50.3% were in the calcemia and phosphatemia range, respectively. The average PTH was 601 and the median 437 pg/ml. 50.5% had PTH in range, 15% below 150 pg/ml and 34.5% above 600 pg/ml. In relation to medication, 47% of the patients received calcium chelators with extreme use ranging from 4.5-8% in some centers to 83-94%. 28.8% received Sevelamer, calcitriol 38%, paricalcitol 11% and cinacalcet 20%, its use being variable according to the centers from 3% to 52%. Conclusion: the presence of secondary hyperpartyroidism was more frequent than desired, probably linked to the difficulty in the adequate use of medications.

Residual urinary output in high body mass index individuals on chronic hemodialysis: A disregarded life vest?

AIM: To assess residual diuresis and diverse variables according to body mass index (BMI). METHODS: Cross-sectional study (n = 57), with 3 groups. Group A: BMI < 25, n = 22; Group B: BMI 25-30, n = 15; Group C: BMI > 30, n = 20. Diuresis, hematocrit, albumin, C-reactive protein, Malnutrition inflammatory score, Pro-BNP, Troponin T, leptin and insulin levels are expressed as median and ranges (r). RESULTS: Albumin (g/dL): GA vs GC, 3.70 (r2.20-4.90) vs 3.85 (r3.40-4.90), P = 0.02. Diuresis (mL/d): GA 690 (r0-1780); GB 660 (r60-1800); GC 840 (r40-2840). Diuresis GA vs GC, P = 0.01. Leptin (ng/mL): GA vs GC, 3.81 (r0.78-69.60) vs GC, 32.80 (r0.78-124.50), P < 0.001. Insulin (µU/mL): GA vs GB, 7 (r2-44) vs 11.50 (r4-38), P = 0.02; GA vs GC, 7 (r2-44) vs 19.5 (r5-155), P = 0.0001. Troponin T and Pro-BNP levels were not different. Significant correlations: GC, Insulin-UF: ρ = 0.53; P = 0.03; TroponinT-diuresis: ρ = -0.48, P < 0.05; Pro-BNP-diuresis: ρ = -0.39, P < 0.01; Troponin T-ProBNP: ρ = 0.77, P < 0.0001; albumin-Troponin T: ρ = -0.66, P < 0.0001; albumin-ProBNP: ρ = -0.44, P < 0.05. CONCLUSION: High BMI associated positively with higher diuresis and albuminemia, and negatively with TropT and Pro-BNP. High BMI-associated better survival may be explained by better urinary output, lowering cardiovascular stress.