LC endocytosis leads to production of inflammatory cytokines through activation of NF-kappaB. This may be an important mechanism of chronic tubulointerstitial inflammation process commonly seen in multiple myeloma. These findings also point out a potential role by filterable low-molecular-weight proteins, like LCs, in PTC injury during all proteinuric diseases.

We previously demonstrated that light chain (LC) endocytosis by human proximal tubule cells (PTCs) leads to production of cytokines through activation of NF-kappaB. Here, we examined the role of MAPK pathways in these responses using four species of myeloma LCs (kappa(1), kappa(2), kappa(3), and lambda(1)) previously shown to induce cytokine production by PTCs. Among these, kappa(1)-LC, which yielded the strongest cytokine responses, was selected for detailed studies. Activation of MAPKs was probed by Western blot analysis for the active kinases, ERK 1/2, JNK 1/2, and p38 in kappa(1)-LC-exposed human PTCs. To evaluate the functional role of MAPKs in LC-induced cytokine responses, we tested the effects of U-0126, an ERK inhibitor; SP-600125, an inhibitor of JNK; SB-203580, a p38 inhibitor; and curcumin, a JNK-AP-1 inhibitor, all added to media before 4-h exposure to 1.5 mg/ml kappa(1)-LC. IL-6 and monocyte chemotactic protein-1 (MCP-1) were determined by ELISA. Both LC and human serum albumin (HSA) activated ERK, although the HSA effect was weaker. kappa(1)-LC stimulated all three MAPKs, although phosphorylation of ERK was more pronounced and sustained than others. Inhibitors of ERK, JNK, and p38 reduced LC-induced IL-6 and MCP-1 production. These findings suggest that activation of MAPKs plays a role in LC-induced cytokine responses in PTCs. Activation of MAPKs may be involved in cytokine responses induced by other proteins as well as LCs and may be pivotal in the pathophysiology of tubulointerstitial injury in proteinuric diseases.

Objectives:The study aimed to assess the current epidemiology of hypertension, including its prevalence, the awareness of the condition and its treatment and control, in Turkey to evaluate changes in these factors over the last 10 years by comparing the results with the prevalence, awareness, treatment, and control of hypertension in Turkey (PatenT) study data (2003), as well as to assess parameters affecting awareness and the control of hypertension.Methods:The PatenT 2 study was conducted on a representative sample of the Turkish adult population (n = 5437) in 2012. Specifically trained staff performed the data collection. Hypertension was defined as mean SBP or DBP at least 140/90 mmHg, previously diagnosed disease or the use of antihypertensive medication. Awareness and treatment were assessed by self-reporting, and control was defined as SBP/DBP less than 140/90 mmHg.Results:Although the prevalence of hypertension in the PatenT and PatenT 2 surveys was stable at approximately 30%, hypertension awareness, treatment, and control rates have improved in Turkey. Overall, 54.7% of hypertensive patients were aware of their diagnosis in 2012 compared with 40.7% in 2003. The hypertension treatment rate increased from 31.1% in 2003 to 47.4% in 2012, and the control rate in hypertensives increased from 8.1% in 2003 to 28.7% in 2012. The rate of hypertension control in treated patients improved between 2003 (20.7%) and 2012 (53.9%). Awareness of hypertension was positively associated with older age, being a woman, residing in an urban area, a history of parental hypertension, being a nonsmoker, admittance by a physician, presence of diabetes mellitus, and being obese or overweight; it was inversely associated with a higher amount of daily bread consumption. Factors associated with better control of hypertension were younger age, female sex, residing in an urban area, and higher education level in Turkey.Conclusion:Although some progress has been made in recognizing hypertension from 2003 to 2012, there is still a large population of untreated or inadequately treated hypertensives in Turkey. Strengthening of population-based efforts to improve the prevention, early detection, and treatment of hypertension is needed.

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Although long-term kidney recipients have a relatively high prevalence of RTA, it is usually mild and subclinical. Further studies are needed to clarify long-term effects of RTA in kidney recipients.

Mycophenolate mofetil (MMF) has commonly been substituted for azathioprine (AZA) in kidney transplantation and has been shown to have a greater effect on T cell function and also B cell function than AZA. Although immunoglobulin deficiency has been investigated in patients treated with protocols that include AZA, it has not extensively been studied in MMF-based immunosuppressive protocols. To evaluate this effect, we conducted a prospective study and recruited 49 patients. The patients received either AZA- (group 1) or MMF- (group 2) based therapy. A total of 17 patients in group 1 and 24 patients in group 2 completed the study. Immunoglobulin levels were evaluated before and in every month after transplantation for a 6-month period. Total infectious episodes were recorded and evaluated after 6 months in both groups. While no significant differences have been found in group 1, there were significant decreases in IgG, M, and A levels in group 2 after 6 months (IgG: 11.6+/-1.5-6.8+/-2.0 g/L, P<0.0001; IgM: 2.20+/-1.40-1.40+/-1.16 g/L, P=0.02; IgA: 1.40+/-0.70-1.07+/-0.86 g/L P=0.03). Two patients (11.7%) in group 1 and 11 patients in group 2 (45.8%) were found to have at least one low level of immunoglobulin (P=0.03). When the infectious complications were evaluated, the mean number of infection episodes in each patient was 1.3+/-1.6 and 0.5+/-0.7 for the MMF and AZA groups, respectively (P=0.06). Recurrent urinary tract infection developed in eight patients and seven of those were in group 2. In group 2, 7 of 11 patients with low immunoglobulin levels had recurrent urinary tract infection (63%), while no patient who had normal immunoglobulin levels developed any recurrent urinary tract infections (P<0.001). After 6 months, MMF was changed to AZA in these seven patients, who had both recurrent urinary tract infections and low immunoglobulin levels. All but one patient was found to have normal immunoglobulin levels after 3 months of conversion and only two episodes of infection were recorded during this period. We suggest that serum immunoglobulin levels can be monitored in patients taking MMF, and conversion from MMF to AZA may be an alternative for patients with low immunoglobulin levels and recurrent urinary tract infections.

Renal transplantation markedly improved arterial stiffness, while it remained elevated in HD patients at the one-yr follow-up. There was no difference between maintenance HD and RTx groups with respect to impact on LVMi in the one-yr follow-up.

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