In conclusion, obese patients have increased risk for DGF. In the past years, obesity was a risk factor for graft loss, death by CVD, and all-cause mortality. However, for the obese transplanted patient today, the graft and patient survival is the same as that of the nonobese patient.

Progranulin (PGRN) is a cysteine rich secreted protein, expressed in epithelial cells, immune cells, neurons, and adipocytes. It was first identified for its growth factor-like properties, being involved in early embryogenesis and tissue remodeling, acting as an anti-inflammatory molecule. In the central nervous system, PGRN has neurotrophic and neuroprotective actions. There is also evidence of PGRN effects on cancer, contributing to tumor proliferation, invasion and cell survival. Recently, PGRN was recognized as an adipokine related to obesity and insulin resistance, revealing its metabolic function and pro-inflammatory properties. In obesity and type 2 diabetes mellitus, PGRN levels are increased. In renal disease, there is a relevant association, however, it is not known if it could contribute to kidney damage or if it is only a route of PGRN elimination. PGRN is an emerging molecule which demands studies in different fields. Possibly, it plays distinct functions in different tissues/cells and metabolic conditions. Here, we discuss potential mechanisms and recent data of PGRN pro-inflammatory actions, regarding obesity, insulin resistance, type 2 diabetes mellitus and kidney disease.

Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; 2) Albuminuric DKD cases: T2DM patients with urinary albumin excretion (UAE) ≥30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; 3) Diabetic controls: T2DM patients with UAE <30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; and 4) Non-diabetic controls: individuals without T2DM. Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04–83.16) vs. albuminuric cases 57.16 (42.24–67.38), diabetic controls 57.28 (42.08–70.47) and non-diabetic controls 44.54 (41.44–53.32) ng/mL; p<0.001]. Urinary progranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30–16.08) vs. 20.94 (12.35–30.22); diabetic controls 14.06 (9.88–20.82) and non-diabetic controls 13.51 (7.94–24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; p<0.001) and interleukin-6 (r = 0.37; p<0.001) and a negative correlation with eGFR (r = -0.22; p = 0.023). Urinary progranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.

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Metabolic syndrome (MS) has been associated with proteinuria and reduced glomerular filtration rate. Immunosuppressive agents increase the incidence of traditional risk factors for cardiovascular disease (CVD) and have known effects on MS components after kidney transplantation. The purpose of this meta-analysis was to evaluate the impact of MS on relevant outcomes after kidney transplantation. MEDLINE, EMBASE, and Cochrane Library were searched up to November 7, 2015. Papers that compared patients with and without MS and assessed one of the following outcomes, graft loss, death by cardiovascular disease, and all-cause mortality, were included. Of 585 studies identified, five studies including 1269 patients were evaluated. MS was identified as a risk factor for graft loss [relative risk, 3.06; 95% confidence interval (CI), 2.17, 4.32; I² = 0%; P heterogeneity = 0.72] and death by CVD (relative risk, 3.53; 95% CI, 1.27, 9.85; I² = 0%; P heterogeneity = 0.40). Results on the association between MS and all-cause mortality were inconclusive (relative risk, 2.61; 95% CI, 0.70, 9.81; I² = 58%; P heterogeneity = 0.09). Graft loss and death by CVD were associated with the presence of MS after transplantation. Randomized clinical trials should be conducted to define whether interventions on each MS component would result in better outcomes after transplantation.