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Creatinine- vs. cystatin C-based equations compared with 99mTcDTPA scintigraphy to assess glomerular filtration rate in chronic kidney disease.

BACKGROUND In chronic kidney disease (CKD), accurate estimation of the glomerular filtration rate (GFR) is mandatory. Gold standard methods for its estimation are expensive and time-consuming. We compared creatinine- versus cystatin C-based equations to measure GFR, employing (99m)Tc-DTPA scintigraphy as the gold standard. METHODS This was a prospective cross-sectional observational study including 300 subjects. CKD was defined according to K/DOQI guidelines, and patients were separated into groups: stage 1 (G1), n=26; stage 2 (G2), n=52; stage 3 (G3), n=90; stage 4 (G4), n=37; stage 5 (G5), n=60; and control group, n=35. Creatinine-based estimates were from 24-hour creatinine clearance using the Walser formula, Cockcroft-Gault, MDRD-4 and CKD-EPI; cystatin C equations used were Larsson, Larsson modified equation, Grubb and Hoek. RESULTS Age and body mass index were different among groups; proteinuria, hypertension, diabetes and primary glomerulopathies significantly increased as CKD worsened. In the global assessment, CKD-EPI and Hoek gave the highest correlations with (99m)Tc-DTPA: rho=0.826, p<0.001 and rho=0.704, p<0.001, respectively. Most significant linear regressions obtained: CKD-EPI vs. (99m)Tc-DTPA, Hoek vs. (99m)Tc-DTPA and CKD-EPI vs. Hoek. However, important differences emerged when each group was analyzed separately. Best significant correlations obtained with (99m)Tc-DTPA: control group, creatinine clearance rho=0.421, p=0.012; G1, Crockoft-Gault rho=0.588, p=0.003; G2, CKD-EPI rho=0.462, p<0.05; G3, CKD-EPI rho=0.508, p<0.001; G4, Hoek rho=0.618, p<0.001; G5, CKD-EPI rho=0.604, p<0.001. CONCLUSIONS At GFR <60 ml/min, CKD-EPI and Hoek equations appeared to best correlate with (99m)TcDTPA. In controls and at early stages of CKD, creatinine-based equations correlated better with (99m)Tc-DTPA, with CKD-EPI being the one with the best degree of agreement.

Proteinuria: an ignored marker of inflammation and cardiovascular disease in chronic hemodialysis.

Background Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis (HD) patients, the main etiologies being diabetes and hypertension. Cardiac and inflammatory biomarkers are usually employed to assess risk or damage, or during follow-up. Proteinuria is considered a strong predictor of morbidity, a cause of inflammation, oxidative stress, hemodynamic alteration, and progression of chronic kidney disease. However, proteinuria is rarely considered in the clinical assessment of HD patients. Methods This was a concurrent, cohort-observational, cross-sectional study in which 52 chronic HD subjects were divided into three groups according to the degree of proteinuria: Group (G) A: <1 g/day, n = 25; GB: 1–3 g/day, n = 13; GC: >3 g/day, n = 14. Baseline hemoglobin, albuminemia, cholesterol, body mass index, Malnutrition-Inflammatory Score, pro-B-type natriuretic peptide, troponin T, C-reactive protein (CRP), and ultrafiltration rates were analyzed. Results There was no difference between groups in terms of baseline age, gender, hypertension, cause of renal failure, hemoglobin, cholesterol, albumin, CRP levels, cardiac biomarkers, adiponectin, body mass index, or Malnutrition-Inflammatory Score. Time on HD: GA, 34.56 ± 23.3 (range [r]: 6–88); GB, 25.15 ± 19.40 (r: 6–58); GC, 18.21 ± 9.58 (r: 6–74) months; P = 0.048. Proteinuria: GA, 0.33 ± 0.30 (r: 0.0–0.88); GB, 1.66 ± 0.54 (r: 1.03–2.75); GC, 7.18 ± 2.80 (r: 3.04–21.5) g/day; P < 0.001. Mean ultrafiltration rates were significantly different: GA, 2.80 ± 0.73; GB: 1.85 ± 0.96 liters/session; P = 0.003. Fourteen diabetic patients were identified (27%): GA, 3 (12%); GB, 3 (23%); GC, 8 (57%); P = 0.009. A positive and significant correlation was observed between diabetes and proteinuria >3 g/day: rho 0.438, P = 0.027. Although troponin T, pro-B-type natriuretic peptide, adiponectin, and CRP were not different among groups, the positive correlation between troponin T and CRP elevated significantly as proteinuria increased: GA, rho 377, P = 0.063; GB, rho 663, P = 0.013; GC, rho 687, P = 0.007. Conclusion In chronic HD, nephrotic-range proteinuria was significantly higher in diabetic nephropathy patients versus other causes. This was associated with inflammation and cardiac stress and was independent of fluid removal. Proteinuria >3 g/day was associated with shorter time on HD. Whether severe proteinuria is associated with shorter survival in HD, independent of diabetes, is to be determined. Proteinuria should be considered in the assessment of cardiovascular and inflammatory states in HD patients.

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.

In hemodialysis, adiponectin, and pro-brain natriuretic peptide levels may be subjected to variations in body mass index

Adiponectin exerts cardiovascular protective actions, although some studies have shown the opposite. In hemodialysis, obese subjects display lower mortality rates despite hypoadiponectinemia, while higher adiponectin concentrations correlate with an elevated cardiovascular risk in nonobese subjects. The aim of the study is to suggest that adiponectin level variations are associated with differences in the body mass index (BMI). The interplay between adiponectin and pro‐brain natriuretic peptide (Pro‐BNP) levels may vary according to body fat mass. Fifty‐two chronic hemodialysis patients were divided into three groups. Group A, BMI<25 (n=20); Group B, BMI 25 to 30 (n=21), and Group C, BMI>30 (n=11). Diabetics: Group A 10%; Group B 6 29%; Group C 55%, P=0.027. Determinations: Adiponectin, Pro‐BNP, insulin, insulin resistance (HOMA), troponin T, nutritional status, ultrafiltration rates, C‐reactive protein (CRP), vascular accesses, and echocardiography. Group A: adiponectinemia positively and significantly correlated with Pro‐BNP, CRP, and troponin T. As BMI increased, adiponectin, Pro‐BNP, and malnutrition significantly decreased, while insulin, HOMA, and ultrafiltration rates significantly increased. Cardiac restriction was significantly higher in obese patients. In all groups, Pro‐BNP and troponin T displayed a strong positive correlation. In low‐BMI subjects, high Pro‐BNP and adiponectin, low myocardial restriction, and worse nutritional status were prevalent. In obesity, hypoadiponectinemia stimulates cardiac remodeling, cardiac hypertrophy, and decreased stretching, rendering Pro‐BNP levels low despite high ultrafiltration rates. Thus, adiponectin correlates inversely with BMI, probably playing different cardiovascular roles as BMI changes.

Disodium pamidronate for treating severe hypercalcemia in a hemodialysis patient.

Background A 48-year-old man with a recent diagnosis of multiple myeloma and rapidly progressive oliguric end-stage renal disease requiring hemodialysis, presented with a serum calcium concentration of 3.4 mmol/l (13.6 mg/dl).Investigations Serum laboratory analysis, electroencephalogram, MRI of the brain and bone marrow, and kidney biopsies.Diagnosis Hypercalcemia secondary to multiple myeloma.Management Short-term intravenous disodium pamidronate therapy (30 mg daily) and daily monitoring of serum calcium concentration.

Is There a Role for Mammalian Target of Rapamycin Inhibition in Renal Failure due to Mesangioproliferative Nephrotic Syndrome

Primary glomerulonephritis stands as the third most important cause of end-stage renal disease, suggesting that appropriate treatment may not be as effective as intended to be. Moreover, proteinuria, the hallmark of glomerular damage and a prognostic marker of renal damage progression, is frequently resistant to thorough control. In addition, proteinuria may be the common end pathway in which different pathogenetic mechanisms may converge. This explains why immunosuppressive and nonimmunosuppressive approaches are partly not sufficient to halt disease progression. One of the commonest causes of primary glomerulonephritis is mesangioproliferative glomerulonephritis. Among the triggered intracellular pathways involved in mesangial cell proliferation, the mammalian target of rapamycin (mTOR) plays a critical role in cell growth, in turn regulated by many cytokines, disbalanced by the altered glomerulopathy itself. However, when inhibition of mTOR was studied in rodents and in humans with primary glomerulonephritis the results were contradictory. In light of these controversial data, we propose an explanation for these results, to dilucidate under which circumstances mTOR inhibition should be considered to treat glomerular proteinuria and finally to propose mTOR inhibitors to be prospectively assessed in clinical trials in patients with primary mesangioproliferative glomerulonephritis, for which a satisfactory standard immunosuppressive regimen is still pending.

Unilateral breast enlargement due to a high-flux ipsilateral hemodialysis fistula

169 mary vessels moves centrifugally toward the axillary and internal mammary lymph nodes. Approximately 3 percent of the lymph from the breast flows to the internal mammary chain, whereas 97 percent directs to the axillary nodes (1). Thus, an imbalance between a highly vascularized arteriovenous system and poorly developed lymphatic tree could have also contributed to the edema. There still exists no clear definition when a fistula is considered of high-flow. The concept of using the ratio access flow to cardiac output (CO) has been proposed by Pandeya and Lindsay (2); they found that in chronic dialysis subjects, the average access blood flow (Qa) was 1.6 L/min and the average CO was 7.2 L/min, thus describing a normal average Qa /CO ratio of 22 %. Despite surgical correction of the access, the blood flow remained high at 3 L/minute. Published case reports describing high-output cardiac failure all consistently show high-flow AVF with Qa > 2 L/min and Qa/CO ratios greater than 30% to 35 %. More information is required to confirm the plausible concept that high-access flows with elevated Qa/CO ratios may represent a risk factor for heart failure. Most of the reported banding and surgical closure of AVF have occurred when patients developed symptoms of cardiac failure with Qa/CO ratios of > 40%. (3). Studies in upper arm fistulae suggest a normal mean Qa ranging from 1.13 to 1.72 L/min, 15% of patients presenting Qa > 2-2.5 L/min (2) . However, a high flux fistula can result in a hyper-dynamic state that can cause a steal syndrome and end up in high-output heart failure. Steal phenomena can occur in approximately 73% of fistulae and is usually asymptomatic, symptoms appearing when collateral or direct flow is not developed to offset the steal. In a hemodialysis AVF, blood is shunted from a high pressure artery into a low pressure vein, increasing systemic vascular volume (4). The increased cardiac output associated with these fistulae depends upon the size of the communication and the Unilateral breast enlargement due to a high-flux ipsilateral hemodialysis fistula

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

Proteinuria, 99mTc-DTPA Scintigraphy, Creatinine-, Cystatin- and Combined-Based Equations in the Assessment of Chronic KidneyDisease

Background. Precise estimation of the glomerular filtration rate (GFR) and the identification of markers of progression are important. We compared creatinine, cystatin, and combined CKD-EPI equations with 99mTc-DTPA scintigraphy to measure GFR and proteinuria as markers of progression. Methods. Cross-sectional, observational study including 300 subjects. CKD was classified by 99mTc-DTPA scintigraphy. Determinations. Creatinine, 24-hour creatinine clearance, cystatin, Hoek formula, and creatinine, cystatin, and combined CKD-EPI equations. Results. In the global assessment, creatinine CKD-EPI and combined CKD-EPI equations yielded the highest correlations with 99mTc-DTPA: ρ = 0.839, P < 0.0001 and ρ = 0.831, P < 0.0001. Intergroup analysis versus 99mTc-DTPA: control G, creatinine clearance ρ = 0.414, P = 0.013; G3, combined CKD-EPI ρ = 0.5317, P < 0.0001; G4, Hoek ρ = 0.618, P < 0.0001, combined CKD-EPI ρ = 0.4638, P < 0.0001; and G5, creatinine clearance ρ = 0.5414, P < 0.0001, combined CKD-EPI ρ = 0.5288, P < 0.0001. In the global assessment, proteinuria displayed the highest significant correlations with cystatin (ρ = 0.5433, P < 0.0001) and cystatin-based equations (Hoek: ρ = −0.5309, P < 0.0001). When GFR < 60 mL/min: in stage 3, proteinuria-cystatin (ρ = 0.4341, P < 0.0001); proteinuria-Hoek (ρ = −0.4105, P < 0.0001); in stage 4, proteinuria-cystatin (ρ = 0.4877, P < 0.0001); proteinuria-Hoek (ρ = −0.4877, P = 0.0026). Conclusions. At every stage of GFR < 60 mL/min, cystatin-based equations displayed better correlations with 99mTc-DTPA. Proteinuria and cystatin-based equations showed strong associations and high degrees of correlation.

Proteinuria and its relation to diverse biomarkers and body mass index in chronic hemodialysis

Background Certain adipokines exert direct effects on proteinuria, a cardiovascular risk factor ignored in hemodialysis. We measured different adipokines according to body mass index (BMI) in relation to proteinuria. Methods Patients numbered 57: group A (GA), BMI<25, n = 22; GB, BMI 25–30, n = 15; and GC, BMI > 30, n = 20. There were no statistical differences in age, sex, time on dialysis, cause of renal failure, diabetes, hypertension, C-reactive protein, or nutritional status. Measures were taken of 24-hour diuresis and proteinuria, ultrafltration, albumin, pro-brain natriuretic peptide (Pro-BNP), insulin, adiponectin, leptin, and ghrelin. Results Proteinuria was signifcantly higher in GC versus (vs) GA (1.5 g/day, range 0.30–14 vs 0.72 g/day, range 0.1–2.7; P < 0.01) and correlated signifcantly with leptin levels (ρ = 0.47, P < 0.05). In GA, elevated levels of Pro-BNP, adiponectin, and ghrelin were associated with lower degrees of proteinuria. Signifcant correlations were found between adiponectin and leptin (ρ = −0.54, P = 0.03), and adiponectin and Pro-BNP (ρ = 0.59, P = 0.02). Though not signifcant, there were more diabetics in GC (GA four, GB three, GC ten). As BMI increased in GB and GC, Pro-BNP, adiponectin, and ghrelin levels decreased signifcantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were signifcantly elevated in GC vs GA and GB. In GC, ghrelin correlated signifcantly with Pro-BNP (ρ = 0.51, P = 0.03), while leptin correlation with Pro-BNP was inverse and signifcant in GA (ρ = −0.74, P < 0.001) and inverse and nonsignifcant in GB and GC. Conclusion In patients with BMI < 25, higher adiponectin, ghrelin, and Pro-BNP levels were associated with lower proteinuria and leptinemia. In obesity, hyperleptinemia and hyperinsulinemia associated with higher proteinuria; whether decreased adiponectin–ghrelin–ProBNP and/or elevated leptin–insulin levels aggravate proteinuria remains to be determined.