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Hernán Trimarchi,1 Alexis Muryan,2 María-Soledad Raña,1 Pedro Paggi,2 Fernando Lombi,1 Mariano Forrester,1 Vanesa Pomeranz,1 Alejandra Karl,1 Mirta Alonso,2 Pablo Young,3 Mariana Dicugno2 1Department of Nephrology, 2Department of Biochemistry, 3Department of Internal Medicine Services, Hospital Británico de Buenos Aires, Buenos Aires, Argentina 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, ultrafiltration, albumin, pro-brain natriuretic peptide (Pro-BNP), insulin, adiponectin, leptin, and ghrelin. Results: Proteinuria was significantly 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 significantly 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. Significant 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 significant, 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 significantly, while proteinuria, insulin, and homeostasis model assessment of insulin resistance increased. Leptin levels were significantly elevated in GC vs GA and GB. In GC, ghrelin correlated significantly with Pro-BNP (ρ= 0.51, P = 0.03), while leptin correlation with Pro-BNP was inverse and significant in GA (ρ = -0.74, P > 0.001) and inverse and nonsignificant 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. Keywords: proteinuria, adiponectin, ghrelin, leptin, Pro-BNP, hemodialysis, BMI

Hernán Trimarchi1, Alexis Muryan2, Mariana Dicugno2, Pablo Young3, Mariano Forrester1, Fernando Lombi1, Vanesa Pomeranz1, Romina Iriarte1, María Soledad Raña1, Mirta Alonso21Nephrology, 2Biochemistry, 3Internal Medicine Services, Hospital Británico de Buenos Aires, ArgentinaBackground: 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: 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.Keywords: hemodialysis, proteinuria, inflammation, cardiovascular risk

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.

Patients with chronic renal disease are at increased risk for the development of cardiovascular disease, which is the main cause of death in this growing population. Among the risk factors involved, hypertension and proteinuria are major contributors to kidney damage and, if not controlled, may eventually lead to the progression of renal failure and end-stage renal disease. Both proteinuria and hypertension can be primary pathologic events or can appear as complications of other disease processes. Initially, these two factors may operate separately but, as progression ensues, both processes generally combine, potentiating their effects and hastening renal damage. Therefore, strategies to reduce blood pressure and proteinuria are essential in order to slow the worsening of many nephropathies. Therapies that target the renin-angiotensin system offer particular benefit, as hypertension and proteinuria can be precisely reduced with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers. However, with this intervention, plasma renin activity remains high, and although primary endpoints may be controlled, elevated renin concentration can contribute to cardiovascular damage. Aliskiren, a direct renin inhibitor, is the first example of a novel class of antihypertensive drugs with potent antiproteinuric effects, which, alone or combined, can contribute to delaying the progression of kidney disease.