Renal complications of lipodystrophy: A closer look at the natural history of kidney disease.

OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multicentre study, prospective follow-up data were collected from 103 subjects with non-HIV-associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR). Kidney volume was measured. Percutaneous renal biopsies were performed in 9 patients. RESULTS: Seventeen of 37 patients with generalized and 29 of 66 patients with partial lipodystrophy had CKD characterized by proteinuria, of those 12 progressed to renal failure subsequently. The onset of renal complications was significantly earlier in patients with generalized lipodystrophy. Patients with CKD were older and more insulin resistant and had worse metabolic control. Increased kidney volume was associated with poor metabolic control and suppressed leptin levels. Renal biopsies revealed thickening of glomerular basal membranes, mesangial matrix abnormalities, podocyte injury, focal segmental sclerosis, ischaemic changes and tubular abnormalities at various levels. Lipid vacuoles were visualized in electron microscopy images. CONCLUSIONS: CKD is conspicuously frequent in patients with lipodystrophy which has an early onset. Renal involvement appears multifactorial. While poorly controlled diabetes caused by severe insulin resistance may drive the disease in some cases, inherent underlying genetic defects may also lead to cell autonomous mechanisms contributory to the pathogenesis of kidney disease.

Evaluation of nephrotoxicity and prognosis in patients treated with colistin due to hospital-acquired pneumonia.

INTRODUCTION: Colistimethate sodium (CMS) is frequently used in the treatment of nosocomial multidrug-resistant gram-negative infections. Nephrotoxicity is the most important side effect. The aim of this study is to evaluate the effect of colistin on nephrotoxicity and to assess prognosis in patients treated with CMS due to hospital-acquired pneumonia (HAP). MATERIALS AND METHODS: Patients treated with CMS for HAP due to multidrug-resistant Pseudomonas aeruginosa or Acinetobacter baumannii were included in this cohort study. RESULT: We evaluated 281 patients treated with two different brands of CMS whose administration dose is different: imported (n= 58, low dose/kg) and domestic (n= 223, high dose/kg). Nephrotoxicity developed in 175 patients (62.3%). The median age (73 vs. 66 years, p= 0.004) and mortality rates were higher (66.9% vs. 52.8%, p= 0.022) in patients having nephrotoxicity. The patients receiving high dose/kg had higher nephrotoxicity rate (67.7% vs. 41.4%, p< 0.001). The clinical, bacteriological response and mortality rates of the whole group were 52.0%, 61.0%, 61.6%, respectively. The clinical and bacteriological response rates were similar in the different dose groups. Multivariate analysis showed that nephrotoxicity was associated with domestic brand depending on use of high dose (OR= 3.97), advanced age (ß= 0.29, p= 0.008), male gender (OR= 2.60), hypertension (OR= 2.50), red blood cells transfusion (OR= 2.54), absence of acute kidney injury (OR= 10.19), risk stage of RIFLE (OR= 11.9). CONCLUSIONS: Nephrotoxicity is associated with the use of high dose colistin, age, gender, hypertension, red blood cells replacement and RIFLE stage. The mortality rate is higher in patients developing nephrotoxicity.

Recurrent lupus nephritis after transplantation: Clinicopathological evaluation with protocol biopsies.

AIM: Lupus nephritis (LN) is an important complication of systemic lupus erythematosus (SLE). The aim is to use indication and protocol biopsies to determine clinicopathological findings and outcomes of patients with LN undergoing kidney transplantation (KTx). METHODS: Patients who underwent KTx due to LN were retrospectively analyzed. Recurrent LN (RLN) was diagnosed by transplant kidney biopsy. RESULTS: Among 955 KTx patients, 12 patients with LN as the cause of end-stage renal disease were enrolled. Five patients were male. Mean follow-up time was 63 ± 34 months. At the last follow-up visit, mean levels of serum creatinine and proteinuria were 137.0 ± 69.0 µmol/L and 0.26 ± 0.26 g/day, respectively. Eighteen indication and 22 protocol biopsies were performed; 27 biopsies were additionally evaluated by immunofluorescence. In two recipients, subclinical RLN was confirmed by protocol biopsies. Clinical recurrence occurred in four patients. Among patients with RLN, time from diagnosis of LN to KTx was significantly shorter and use of ATG as induction treatment was significantly lower. Graft loss occurred in two recipients who had clinical RLN. Five-year overall graft survival was 85.7%. CONCLUSION: Kidney transplantation is a reasonable option for patients with ESRD secondary to SLE. However, recurrence of LN is common if protocol biopsies are included in post-transplantation surveillance.

Circulating apelin levels are associated with cardiometabolic risk factors in women with previous gestational diabetes.

PURPOSE: Women with previous gestational diabetes mellitus (pGDM) are at high risk for type 2 diabetes and cardiovascular disorders. In this study, we aimed to compare plasma apelin levels between women with and without pGDM, and to investigate the possible association of apelin with cardiometabolic risk factors. METHODS: Among 252 consecutive Caucasian women with GDM being included in a prospective postpartum follow-up protocol, 141 women eligible for the study protocol were enrolled. Control group consisted of 49 age- and body mass index-matched healthy women without pGDM. Circulating apelin, IL-6 and plasminogen activator inhibitor levels, and carotid intima media thickness (IMT) were measured. To evaluate carbohydrate intolerance, 75-g oral glucose tolerance test was performed. Fasting insulin and lipids were measured, and homeostasis model assessment index was calculated. RESULTS: Plasma apelin levels were reduced in women with pGDM (p < 0.001). In multiple regression analysis, apelin was negatively associated with fasting (r (2) 0.090, ß -0.273, p = 0.001) and post-load glucose (r (2) 0.061, ß -0.187, p = 0.022), serum IL-6 (r (2) 0.082, ß -0.234, p = 0.002), and carotid IMT (r (2) 0.057, ß -0.168, p = 0.033). CONCLUSIONS: Our results suggested that suppressed apelin levels were associated with increased cardiovascular risk in women with pGDM.

Rare cause of weight loss in a kidney transplant recipient: iron overload.

Various reasons such as malignancies and chronic infections may cause weight loss in kidney transplant patients. In this report, iron overload as a rare cause of weight loss in a kidney transplant patient is presented. Forty-seven-year-old male patient who transplanted from a deceased donor 5 years ago was hospitalized because of 20 kg of weight loss. In medical history, he had history of hemodialysis for 89 months and received 100-300 mg of intravenous iron therapy per week before transplantation and transfused eight units of blood. In physical examination, weight and height were 45 kg and 185 cm, respectively. Respiratory and cardiac auscultation was normal. Laboratory results revealed as follow: glucose 76 mg/dL, urea 60 mg/dL, creatinine 1.35 mg/dL, aspartate aminotransferase 74 U/L, alanine aminotransferase 77 U/L, C-reactive protein 2.59 mg/dL, albumin 3.3 g/dL, globulin 3.4 g/dL, white blood cells 3200/mm(3), hemoglobin 13.1 g/dL and platelets 190,000/mm(3). Chest and abdominal tomography didn't reveal any pathology. Portal Doppler ultrasound showed signs of early cirrhosis. Viral and autoimmune hepatitis markers were negative. Ferritin was 5300 ng/mL and transferrin saturation was 82%. In liver biopsy, hemosiderosis was diagnosed and heterozygous H63D gene mutation was detected. Totally, 19 units of phlebotomy were performed. Liver function tests and serum ferritin decreased gradually. At outpatient follow-up in 6 months, he returned to former weight. In conclusion, there can be several causes of weight loss in kidney transplant patients. Iron overload can come across as a rare cause of weight loss. In these patients, ferritin levels should be checked and diagnosis should be clarified by liver biopsy and gene mutation analysis.

Genetic characterization of Toxoplasma gondii strains isolated from humans living in Izmir, Türkiye.

PURPOSE: Toxoplasma gondii is an obligate intracellular zoonotic parasite that can infect all warm-blooded animals, including humans. Currently, clinical findings of toxoplasmosis are being related to T. gondii strains such as Type I genotype may cause high pathogenicity and Type II genotype causes a milder clinical presentation. We have showed in our previous that Type II genotype is the most frequent strain detected in stray cats and wild birds living in natural life of Izmir. The aim of this study was to assess toxoplasmosis seroprevalence in immunocompromised patients, investigate the presence of T. gondii DNA in their blood samples, and genotype the PCR positive ones. METHODS: The 42 buffy-coat and serum samples were collected from immunocompromised patients who were from various clinics. Thereafter, Real-Time PCR targeting RE gene of T. gondii was performed with DNA samples obtained from buffy-coat samples. Genotyping was performed by sequencing of GRA6 and GRA7 gene regions of positive DNA samples obtained from tissues of bioassay and PCR positive samples. RESULTS: According to Real-Time PCR results, T. gondii DNA was detected in 23.8% (10/42) samples. Among these 10 samples, two samples were determined as T. gondii Type II genotype. Anti-Toxoplasma IgG antibodies were detected in 28.57% (12/42) samples. CONCLUSIONS: Overall, the detection of Type II genotype in humans in Izmir province suggested that T. gondii infection in humans, stray cats, and wild animals may be associated to each other in terms of transmission.

Is Serum Magnesium Level Associated With Serum Lipid Levels in Kidney Transplant Recipients?

BACKGROUND: Magnesium (Mg) is key in diabetes mellitus, hyperlipidemia, and cardiovascular disease. METHODS: This is a retrospective cross-sectional study including 103 kidney transplant recipients. Patients aged under 18 years, patients treated with Mg supplementation, antihyperlipidemic agents, or diuretics, and patients with active infection or malignancy were not enrolled. Patients were divided into 2 groups according to median serum Mg level. The atherogenic index of plasma was calculated by a logarithmic transformation of the number acquired by dividing the molar concentrations of serum triglyceride by high-density lipoprotein value. RESULTS: The mean serum Mg level was 1.91 ± 0.28 mg/dL. Six patients (5.8%) had hypomagnesemia (Mg <1.5 mg/dL), and 2 (1.9%) had hypermagnesemia (Mg >2.6 mg/dL). Serum Mg level was negatively correlated with body mass index, estimated glomerular filtration rate (eGFR), and tacrolimus trough level and positively correlated with levels of phosphorus, total cholesterol, and low-density lipoprotein (LDL-C). There was no correlation between serum Mg and triglyceride, high-density lipoprotein, atherogenic index of plasma, and cyclosporin A trough level. Patients with Mg >1.87 mg/dL had lower eGFR, tacrolimus, and cyclosporin A trough level and higher total cholesterol and LDL-C compared to those with Mg ≤1.87 mg/dL. In adjusted ordinal analysis, eGFR (hazard ratio (HR): 0.981, 95% CI 0.964-0.999, P = .036) and total cholesterol (HR: 1.015, 95% CI 1.004-1.027, P = .008) were independently associated with serum Mg. In multivariate linear regression analysis, serum Mg level was independently associated with LDL-C (ß = .296, t = 3.079, P = .003) and total cholesterol (ß = .295, t = 3.075, P = .003). CONCLUSION: Serum Mg level may have an important impact on dyslipidemia in kidney transplant recipients.

New-Onset Hypercalcemia After Renal Transplant: An Infectious Etiology Beyond Persistent Hyperparathyroidism.

Pneumocystis jirovecii pneumonia is an opportunistic infection in kidney transplant recipients. It may be complicated by hypercalcemia. Here, we discuss a 59-year-old man who presented with respiratory symptoms and hypercalcemia. He had undergone a deceased donor kidney transplant 2 years previously. The patient had persistent hyperparathyroidism, but his serum calcium level was normal. At the time of admission, his serum calcium level had increased and his parathyroid hormone level was suppressed. He was diagnosed with Pneumocystis jirovecii pneumonia. Serum calcium and parathyroid hormone levels returned to baseline values after treatment. Pneumocystis jirovecii pneumonia is an important infection that can present with hypercalcemia among kidney transplant recipients.

Evaluation of postpartum carbohydrate intolerance and cardiovascular risk factors in women with gestational diabetes.

We aimed to evaluate the predictors of subsequent development of postpartum carbohydrate intolerance, metabolic syndrome and cardiovascular risk factors in women with previous GDM. Two hundred fifty-two consecutive women with GDM were enrolled. After exclusion of women who did not attend to the hospital for follow-up visits for minimum 1 year, data of 195 patients were evaluated. Seventy-one lean women with negative screening for GDM were included as a control group. The prevalence of diabetes, impaired glucose tolerance and impaired fasting glucose and metabolic syndrome was significantly higher in women with previous GDM than healthy controls. Women with previous GDM were more insulin resistant, had an atherogenic lipid profile and increased carotid IMT. The most important predictors of postpartum diabetes were the need for insulin treatment during index pregnancy and glucose values on antepartum OGTT. Among women with previous GDM, the development of postpartum diabetes and metabolic syndrome was associated with increased carotid IMT. Our data show that women with previous GDM are at high risk for developing carbohydrate intolerance, metabolic syndrome and atherosclerosis. Antepartum prediction of high risk subjects for the subsequent development of postpartum carbohydrate intolerance and metabolic syndrome seems to be vital to prevent cardiovascular outcomes.

A histopathological scoring and grading system to predict outcome for patients with AA amyloidosis.

PURPOSE: Renal involvement is associated with significant morbidity and mortality in AA amyloidosis. Extend of amyloid deposition in kidney biopsies may be predictive for clinical manifestations and outcomes. The aim of our study is to assess clinical features of patients with biopsy-proven renal AA amyloidosis and to evaluate the relationship between histopathological scoring and grading of renal amyloid deposition with clinical findings and outcomes. METHODS: The study included 86 patients who were diagnosed with renal AA amyloidosis. The demographic and clinical features at the time of biopsy and follow-up data were retrospectively collected. Amyloid deposition in glomeruli, interstitium, vessels and tubulointerstitial findings were scored and renal amyloid prognostic score (RAPS) was assigned by adding all scores. RAPS was further divided into three grades (RAPS grade I, II, III). RESULTS: Median age was 50 (36-59) years. Familial Mediterranean fever was the leading cause. RAPS grade and interstitial inflammatory infiltration were associated with baseline eGFR and glomerular amyloid deposition was associated with proteinuria. During the follow-up period (median 50 months), 39 patients developed ESRD. Extensive (involving > 50%) glomerular amyloid deposition, baseline eGFR and proteinuria were independent risk factors for progression to end stage renal disease. Death censored renal survival was significantly lower among patients with RAPS grade III compared to those with RAPS grade I and II. Patient survival rate was not different according to RAPS grade. CONCLUSIONS: Degree of renal amyloid accumulation is associated with renal function and outcome. The scoring and grading system may be predictive in clinical outcome and contribute to understanding of disease mechanism.

Impact of body mass index on short-term and long-term survival in prevalent hemodialysis patients.

INTRODUCTION: Numerous studies showed that higher body mass index (BMI) is associated with better survival in hemodialysis (HD) patients. Most of them evaluated short-term mortality. It has been suggested that presence of inflammation may be a key modifier of relationship between BMI and mortality in incident HD patients. We examined whether presence of inflammation modifies the association between BMI and mortality in both short-term and long-term follow-up in a large group of prevalent HD patients. METHODS: A total of 3.252 HD patients from 41 HD centers were enrolled; the patients were divided into quartiles based on time-averaged BMI (Q1 < 21.5, Q2 21.5 to <24.3, Q3 24.3 to <27.4, Q4 ≥ 27.4 kg/m2 ). Inflammation status was defined as present (inflamed) (C-reactive protein (CRP) ≥1.0 mg/dL and/or serum albumin ≤3.5 g/dL) or absent (noninflamed). FINDINGS: During 7 years of follow-up 1386 patients (42.6%) died. Compared to noninflamed patients, inflamed patients in the lowest BMI quartile showed 5-fold increased risk for mortality in the short-term (95% confidence interval [CI] 2.82-9.22, P < 0.001) and 3-fold in the long-term (95%CI 2.42-4.27, P < 0.001) compared to the highest BMI quartile. Whereas, inflamed patients in the highest BMI quartile experienced 2-fold increased risk in short-term (95%CI 1.17-3.74, P = 0.01) and 1.68-fold increased risk in long-term (95%CI 1.30-2.18, P < 0.001) than in noninflamed patients. The protective effect of BMI for overall mortality was present in all age groups, in both genders, in patient with and without diabetes. BMI was not a mortality predictor in patients with HD duration more than 76 months at baseline. The protective effect of BMI was observed in all albumin tertiles. In patients in the lowest CRP tertile, BMI was not associated with mortality. DISCUSSION: Higher BMI is associated with lower short-term and long-term mortality risk, especially in patients with inflammation in a prevalent HD population.

Cytomegalovirus disease in renal transplant recipients: a single-center experience.

UNLABELLED: Cytomegalovirus (CMV) disease is an important complication and an independent risk factor for acute rejection and recipient morbidity-mortality. The aim of this study was to review the results of CMV disease in renal transplant recipients. METHOD: We have retrospectively analyzed CMV disease in 120 renal transplant recipients and recorded the demographic features, clinical manifestations, and immunosuppressive regimens. RESULTS: Twenty-nine recipients (24.1%) developed CMV disease after a median interval of 2.8 +/- 2,6 months from transplantation. CMV disease developed in 36.3% of recipients who received basiliximab as induction therapy and 21.4% of recipients who were treated with anti-thymocyte globulin (ATG). The most commonly used immunosuppressive regimen was cyclosporine-A (CsA)-based (79.3%). The mean cumulative steroid dose until the diagnosis was 3,600 mg methyl prednisolone per patient. Malaise, fever, and diarrhea were the most common symptoms. Gastritis, pneumonia, and transaminitis were the most commonly seen end-organ involvements. Frequent laboratory findings were leukopenia (34.5%), increased serum creatinine level (34.5%), and leukocytosis (20.7%). We performed renal biopsy to seven patients and detected acute rejection in four patients. In 25 patients, immunosuppressive treatment was modified. Relapsing CMV disease was seen in seven patients. CONCLUSION: In our study, CMV disease was seen in recipients who were treated with basiliximab, a finding similar to recipients who were treated with ATG.

Is There an Increased Arterial Stiffness in Patients with Primary Sjögren's Syndrome?

OBJECTIVE: Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease that primarily affects the salivary and lacrimal glands. Arterial stiffness is one of the earliest detectable manifestations of adverse structural and functional changes within the vessel wall. The aim of this study was to evaluate the relationship between arterial stiffness and pSS. METHODS: In this study, 75 female patients with pSS who fulfilled the American European Consensus Criteria for Sjögren's syndrome, were included. A total of 68 age-, sex- and body mass index-matched subjects were recruited as the control population. Arterial stiffness was assessed by measurement of the carotid-femoral pulse wave velocity (PWV). RESULTS: The mean age of the patients was 54.0±9.3 years and the median duration of the disease was 10 years. Compared with the control subjects, patients with pSS had a higher mean PWV (8.2±1.5 m/s vs. 7.5±1.4 m/s; p=0.01). Correlation analysis showed that the PWV was positively correlated with age, body mass index, serum cholesterol, low-density lipoprotein (LDL) and C-reactive protein levels, blood pressure, mean arterial pressure (MAP), pulse pressure and left ventricular mass index. A multiple linear regression analysis revealed that arterial stiffness was associated with age, MAP and LDL levels in pSS patients. CONCLUSION: Although patients with pSS appear to have increased arterial stiffness, risk factors associated with arterial stiffness in these patients are similar to the general population. However, we cannot exclude the possibility that a higher PWV in pSS patients is caused, not by pSS itself, but by the use of steroids, hypertension and dyslipidemia.

The effect of hypercalcemia on allograft calcification after kidney transplantation.

PURPOSE: Persistent hypercalcemia after kidney transplantation (KTx) may cause nephrocalcinosis and graft dysfunction. The aim of this study was to evaluate patients with hypercalcemia and assess its effect on tubulointerstitial calcification. METHODS: A total of 247 recipients were enrolled. Transient and persistent hypercalcemia was defined as hypercalcemia (corrected serum calcium >10.2 mg/dL) persisting for 6 and 12 months after KTx, respectively. The severity of calcification in the 0-h, 6- and 12-month protocol biopsies of patients with transient (n = 8) and persistent hypercalcemia (n = 20) was compared with a matched control group (n = 28). RESULTS: Twenty-eight patients were hypercalcemic at 6 months posttransplantation. Serum calcium levels were normalized in eight of them at the end of the first year. Dialysis duration was a positive predictor of persistent hypercalcemia. Tubulointerstitial calcification was detected in 70.6 and 90 % of patients with persistent hypercalcemia at 6 and 12 months posttransplantation, respectively. In 20 % of patients with transient hypercalcemia, severity of calcification regressed at 12 months posttransplantation along with normalization of serum calcium levels. Graft functions and histopathological findings (ci, ct, ci + ct, cv, ah, percentage of sclerotic glomeruli) were not different at 6 and 12 months posttransplantation. CONCLUSIONS: Hypercalcemia and persistent hyperparathyroidism are not rare after KTx. Tubulointerstitial calcification is more common and progressive among patients with persistent hypercalcemia. Normalization of calcium levels may contribute to regression of calcification in some patients.

Comparison of Turkish and US haemodialysis patient mortality rates: an observational cohort study.

BACKGROUND: There are significant differences between countries in the mortality rates of haemodialysis (HD) patients. The extent of these differences and possible contributing factors are worthy of investigation. METHODS: As of March 2009, all patients undergoing HD or haemodiafiltration for >3 months (n = 4041) in the Turkish clinics of the NephroCare network were enrolled. Data were prospectively collected for 2 years through the European Clinical Dialysis Database. Mean age ± standard deviation was 58.7 ± 14.7 years, 45.9% were female and 22.9% were diabetic. Comparison with US data was performed by applying an indirect standardization technique, using specific mortality rates for patients on HD by age, gender, race and primary diagnosis as provided by the 2012 US Renal Data System Annual Data Report as reference. RESULTS: The crude mortality rate in Turkey was 95.1 per 1000 patient-years. Compared with the US reference population, the annual mortality rate for Turkey was significantly lower, irrespective of gender, age and diabetes. After adjustments for age, gender and diabetes, the mortality risk in the Turkish cohort was 50% lower than US whites [95% confidence interval (CI) 0.46-0.54, P < 0.001], 44% lower than US African-Americans (95% CI 0.52-0.61, P < 0.001) and 20% lower than Asian-Americans (95% CI 0.74-0.86, P < 0.05). CONCLUSIONS: The annual mortality rate of prevalent HD patients was found to be significantly lower in the studied Turkish cohort compared with that published by the US Renal Data System Annual Data Report. Differences in practice patterns may contribute to the divergence.

Diagnostic and therapeutic efficacy of double-balloon endoscopy in patients with small intestinal diseases: single-center experience in 513 procedures.

BACKGROUND/AIMS: Double-balloon endoscopy (DBE) is a technique that enables the evaluation and treatment of small intestinal diseases. The aim of the study was to evaluate the indications, therapeutic interventions, complications, and safety and to describe the experience with DBE in Turkish patients. MATERIALS AND METHODS: Four hundred twenty consecutive patients undergoing DBE were included in our study. Demographic features, indications, diagnostic findings, therapeutic interventions, complications, and technical aspects of the procedure were recorded. A total of 513 DBEs were carried out. RESULTS: In all, 420 patients underwent a total of 513 DBE procedures (369 (72%) oral and 144 (28%) anal). The most common clinical indications were obscure bleeding (26%), abdominal pain (25.2%), anemia (20%), chronic diarrhea (10.5%), and inflammatory bowel diseases (5.2%). A proper diagnosis was obtained or confirmed in 222 of 420 patients (52.3%). Ulcers/erosions (23.6%), vascular lesions (8.1%), and polyps/tumors (7.4%) represented the most common endoscopic findings. Perforation occurred in one patient as a complication after polypectomy. No major complications due to sedation occurred. CONCLUSION: Double-balloon endoscopy is effective for the diagnosis and treatment of small intestinal diseases. Therapeutic interventions carried out by DBE seem to be useful and safe.

Correlation between serum YKL-40 (chitinase-3-like protein 1) level and proteinuria in renal transplant recipients.

BACKGROUND: YKL-40 (chitinase-3-like protein 1) is a novel inflammation and endothelial dysfunction biomarker. Although YKL-40 is associated with albuminuria and predicts cardiovascular morbidity and mortality in a non-uremic population, it's status is not known in renal transplant recipients. The aim of this study was to investigate plausible links between serum YKL-40 and proteinuria. MATERIAL AND METHODS: A total of 110 renal transplant recipients were included in this study. The level of proteinuria was calculated from spot urine using the protein/creatinine ratio. The estimated glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Serum YKL-40 was determined by ELISA (R&D Systems, USA). RESULTS: The mean patient age was 40.5 ± 10 years. The mean YKL-40, GFR, and proteinuria levels were 66 ± 46 ng/ml, 49 ± 24 ml/min/1.73 m2, and 0.77 ± 1.15 g/day, respectively. Increases in the YKL-40 tertiles were correlated with increases in proteinuria and C-reactive protein and decreases in the GFR and serum albumin. An adjusted linear regression analysis demonstrated that the YKL-40 level (t=3.28, P=0.001), GFR (t=-3.00, P=0.003), and systolic blood pressure (t=2.51, P=0.01) were independently associated with proteinuria. CONCLUSIONS: This is the first study to show that increased serum YKL-40 levels are independently associated with proteinuria in renal transplant recipients. YKL-40 may be responsible for the pathogenesis of cardiovascular injury in this patient population.

Insulin need in gestational diabetes is associated with a worse cardiovascular risk profile after pregnancy.

OBJECTIVE: Women with gestational diabetes mellitus (GDM) treated with insulin are more likely to develop type 2 diabetes after pregnancy compared to mild GDM cases treated with medical nutrition treatment (MNT) alone. We aimed to compare levels of subclinical atherosclerosis markers in women with previous GDM treated with insulin and MNT alone. METHODS: Eighty-one women with previous GDM (45 treated with insulin, 36 treated with MNT) and 35 age-matched lean controls were included. Fasting glucose, insulin and lipids, circulating fibrinogen, CRP, PAI-1 and IL-6 levels were assayed. Carotid intima media thickness (IMT) was measured. RESULTS: Women with previous GDM treated with insulin in pregnancy had significantly higher fasting glucose, plasma PAI-1 levels and carotid IMT compared to women treated with MNT alone. In multiple regression analysis, insulin need in pregnancy was associated with increased carotid IMT and plasma PAI-1 levels (corrected for age, BMI, postpartum duration, fasting glucose and lipids; model r(2)=0.132; beta=0.297, p=0.014 for carotid IMT; model r(2)=0.198; beta=0.345, p=0.003 for PAI-1). CONCLUSION: Women with previous GDM treated with insulin in pregnancy had a worse cardiovascular risk profile compared to mild GDM patients. An intensive preventive approach for cardiovascular disorders is particularly essential for this subgroup of women.

Increased osteoprotegerin levels in women with previous gestational diabetes developing metabolic syndrome.

Osteoprotegerin (OPG), a novel soluble member of tumour necrosis factor receptor superfamily, has been shown to link cardiovascular disorders. The aim of this study is to investigate the potential relationship between serum OPG levels, cardiovascular risk factors and metabolic syndrome in a relatively large group of women with previous GDM. In this cross-sectional case-control study, 128 women with previous GDM and 67 age-matched controls were enrolled. Subjects were evaluated for the diagnosis of metabolic syndrome according to the criteria of the American Heart Association (AHA). Fasting glucose, insulin, serum lipids, CRP and OPG were assayed. HOMA score was calculated. Carotid intima media thickness (IMT) was measured. There was no significant increase in OPG levels in women with previous GDM when compared to controls. On the other hand, women with previous GDM developing metabolic syndrome had higher OPG levels than those without metabolic syndrome and healthy controls. Serum OPG levels were associated with obesity, insulin resistance, serum CRP and carotid IMT. Serum OPG is related to cardiovascular risk factors and metabolic syndrome, and might be involved in the development of cardiovascular disorders in women with previous GDM.

Plasma thrombin-activatable fibrinolysis inhibitor levels are not associated with glucose intolerance and subclinical atherosclerosis in women with previous gestational diabetes.

We aimed to determine plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen levels in women with previous gestational diabetes mellitus (GDM) and to evaluate the possible association of plasma TAFI with glucose intolerance and markers of subclinical atherosclerosis. This cross-sectional study was performed in 111 women with previous GDM and 60 controls. Glucose intolerance was evaluated. Homeostasis model assessment score was calculated. Circulating lipids, interleukin-6, matrix metalloproteinase-1, fibrinogen, plasminogen activator inhibitor-1, and TAFI antigen levels were assayed. Carotid intima media thickness (IMT) was measured. Women with previous GDM had increased levels of atherosclerosis markers and carotid IMT. On the other hand, plasma TAFI antigen levels were similar (P = .395). Thrombin-activatable fibrinolysis inhibitor was not associated with the indices of insulin resistance, glucose intolerance, markers of atherosclerosis, and carotid IMT. Our data demonstrated that plasma TAFI was not altered in women with previous GDM. TAFI was not associated with glucose intolerance and subclinical atherosclerosis.