Tolga Yildirim

Major Barriers against Renin–Angiotensin–Aldosterone System Blocker Use in Chronic Kidney Disease Stages 3–5 in Clinical Practice: A Safety Concern?

Renin–angiotensin–aldosterone system (RAAS) blockers are underutilized in patients with chronic kidney disease (CKD). We aimed to determine barriers against the use of RAAS blockers in these patients. Patients with stage 3–5 CKD referred to Hacettepe University Hospital Nephrology Unit during a 1 year period were evaluated for RAAS blocker use. Two hundred and seventy-nine patients (166 male, 113 female) were analyzed. The mean age of the patients was 56.7 ± 15.2 years, mean serum creatinine was 2.45 ± 1.44 mg/dL, and mean glomerular filtration rate was 33.3 ± 15.1 mL/min. The mean follow-up time was 22.0 ± 21.9 months and the clinical visit number was 4.0 ± 3.5. Angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers were used by 68.8% of all patients and 67.7% of diabetic patients at the time of analysis. In 82.1% of patients, RAAS blockers had either been used earlier or were being used. Hyperkalemia was the principal reason for both not starting and also discontinuing these drugs in patients with CKD. In 37.4% of patients, reasons for not starting RAAS blockers were unclear. This study showed that hyperkalemia is the major barrier against the use of RAAS blockers in patients with CKD. There was, however, a subset of patients who did not receive RAAS blockers even without clear contraindications.

Daily Sodium Intake in Chronic Kidney Disease Patients during Nephrology Clinic Follow-Up: An Observational Study with 24-Hour Urine Sodium Measurement

Objective: To determine daily sodium intake in ‘real practice’ in a large group of chronic kidney disease (CKD) patients who were under regular follow-up in a nephrology clinic. Methods: A total of 373 consecutive outpatients with CKD stages 1–5 (not on dialysis; men: 52.3%, mean age: 51.6 ± 15.4 years) were included in the study. All patients had at least 3 or more nephrology visits and received information on reducing their sodium intake. Data for systolic and diastolic blood pressure, number of antihypertensive medications and 2 consecutive 24-hour urinary sodium levels were obtained from the patients’ medical records. Results: The mean 24-hour urinary sodium levels of 2 consecutive urine samples were 168.8 ± 70.3 and 169.3 ± 67.4 mEq/day (p > 0.05). Only 14.7% of the patients had a sodium excretion <100 mmol/day. There was no difference in daily sodium intake from stages 1 to 4, but it was significantly lower in stage 5 (126.6 ± 60.5 mEq/day, p < 0.05). No relation was found between 24-hour urinary sodium output, number of antihypertensives or thiazide use. Conclusions: This study showed that almost 85% of CKD patients under regular nephrologic care were consuming more sodium than the recommended level. More robust measures should be devised to increase patient and physician compliance with reducing sodium intake in CKD.

An Uninvestigated Risk Factor for Contrast-Induced Nephropathy in Chronic Kidney Disease: Proteinuria

Background: Contrast-induced nephropathy (CIN) is one of the most frequent causes of acute renal failure in hospitalized patients with the incremental use of contrast media. We aimed to investigate whether proteinuria may act as a risk factor for CIN in patients with chronic kidney disease. Methods: Seventy hospitalized patients (37 men, 33 women) with chronic kidney disease, proteinuria, and/or estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2, who were exposed to contrast media were investigated prospectively. Thirty patients were diabetic. All patients received prophylaxis against CIN with acetylcysteine and 0.9% intravenous saline. CIN is defined as either a 25% higher increase in serum creatinine (sCr) from the baseline levels or a 0.5 mg/dL increase in sCr at 72 h after contrast media exposure. Results: CIN was detected in 26 (37.1%) patients. Advanced age, diabetes, heart failure, anemia, baseline sCr of >1.5 mg/dL, baseline eGFR of <60 mL/min/1.73 m2, proteinuria of ≥1 g/day, hypoalbuminemia, and the volume of contrast media of ≥100 mL correlated significantly with CIN. The frequency of CIN was significantly higher in patients with proteinuria of ≥1 g/day compared to patients with proteinuria of <1 g/day (p = 0.009). Conclusion: Proteinuria may be a new risk factor for the development of CIN in patients with chronic kidney disease.

Elevated urinary angiotensinogen a marker of intrarenal renin angiotensin system in hypertensive renal transplant recipients: does it play a role in development of proteinuria in hypertensive renal transplant patients?

The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with hypertension and proteinuria in renal transplant recipients. Sixty‐nine nondiabetic renal transplant recipients (39 male, mean age: 36.3 ± 11.5 years) were included in this study. All patients were in stable condition with GFR greater than 30 ml/min/1.73 m2; (MDRD). Hypertension was defined to be present if there was a recorded diagnosis of hypertension, systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg according to ambulatory blood pressure monitoring. None of the hypertensive patients were receiving RAS blockers. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT‐ELISA, urinary creatinine and protein levels. The demographic properties and laboratory findings were similar between hypertensive and normotensive transplant recipients. Urinary AGT–creatinine ratio (UAGT/UCre) was significantly higher in hypertensive patients compared with the normotensives (8.98 ± 6.89 μg/g vs. 5.48 ± 3.33 μg/g; P = 0.037). Importantly, a significantly positive correlation was found between UAGT/Ucre levels and proteinuria in hypertensive patients (P = 0.01, r = 0.405). Local intrarenal RAS probably plays an important role in the development of hypertension and proteinuria in renal transplant recipients.

Blood pressure measurements, blood pressure variability and endothelial function in renal transplant recipients.

Abstract Background/Aims: Hypertension is an important cardiovascular risk factor in renal transplant recipients. Elevated blood pressure variability (BPV) during 24-h ambulatory blood pressure monitoring (ABPM) is associated with increased risk of target organ damage and cardiovascular events, independent of mean blood pressure levels. We aimed to evaluate the relationship between endothelial function, blood pressure levels obtained by various measurement methods, and BPV in renal transplant recipients. Methods: In total, 73 hypertensive renal transplant recipients were included in the study. Office blood pressure measurements, central blood pressure measurements, home blood pressure measurements and 24-h ABPM were obtained from the subjects. BPV was calculated using the average real variability index. All patients underwent brachial flow-mediated vasodilatation tests. Predictive values of blood pressures obtained by different measurement techniques and BPV on endothelial functions were investigated. Results: Endothelial dysfunction was present in 68.5% of the patients. No difference was found between the group with and without endothelial dysfunction with regard to office systolic or diastolic blood pressure, central blood pressure or home systolic blood pressure. In the group with endothelial dysfunction, 24-h ambulatory systolic blood pressure and night-time ambulatory systolic blood pressure were higher. In patients with endothelial dysfunction, the 24-h systolic, diastolic and mean BPV were all higher. There was also a negative correlation between the percentage of flow-mediated vasodilatation with 24-h mean and systolic BPV. Conclusion: Patients with endothelial dysfunction had significantly higher ambulatory blood pressure values and higher BPV. There was a significant negative correlation between endothelial function and BPV.

Lansoprazole-induced acute allergic interstitial nephritis in a renal transplant recipient: a case report

Drug-induced interstitial nephritis is one of the causes of graft dysfunction in renal transplant recipients. Although commonly implicated as a cause of drug-induced interstitial nephritis in the general population, proton pump inhibitor-induced interstitial nephritis has not yet been reported in renal transplant recipients. Trimethoprim-sulfamethoxazole is responsible for most cases of interstitial nephritis in this population. Here, we describe the first case of proton pump inhibitor-related interstitial nephritis in a renal transplant recipient.

The relation between urinary angiotensinogen and proteinuria in renal AA amyloidosis patients.

Objective: The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with proteinuria in patients with renal AA amyloidosis. Methods: Thirty-two patients with renal AA amyloidosis (19 male, mean age: 45 ± 13 years) and sixteen healthy controls (5 male, mean age: 32 ± 5 years) were included in this study. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT-ELISA, urinary creatinine and protein levels. Logarithmic transformations of urinary AGT-creatinine ratio log(UAGT/Ucre) and urinary protein-to-creatinine ratio (UPCR) were done to obtain the normal distributions of these parameters. Results: Log(UAGT/UCre) was significantly higher in patients compared with the controls (1.88 ± 0.92 µg/g vs. 1.25 ± 0.70 µg/g; p = 0.023). Importantly a significantly positive correlation was found between log(UAGT/Ucre) and logUPCR in patients (r = 0.595, p = 0.006). Conclusions: Urinary AGT levels are higher in renal AA amyloidosis patients than in controls. Also, there is a significant positive correlation between urinary AGT and proteinuria in renal AA amyloidosis.

AA type renal amyloidosis secondary to FMF: a long-term follow-up in two patients

Renal amyloidosis, which leads to renal failure, is the most important long-term complication of familial Mediterranean fever (FMF). Resolution of nephrotic syndrome secondary to amyloidosis in FMF following colchicine treatment has rarely been reported. We describe two patients with FMF and nephrotic syndrome. These patients were treated with colchicine 1.5 mg/day and had a complete remission of nephrotic syndrome with a stable clinical course over 30 years. To our knowledge, our patients have the longest follow-up time without proteinuria.

Evaluation of sarcopenia in renal transplant recipients.

Background: Chronic kidney disease can lead to sarcopenia; however, no study has described sarcopenia in the patients undergoing renal transplantation. Objectives: The aim of the present study was to assess the prevalence of sarcopenia in renal transplant recipients (RTR) and to evaluate the demographic and metabolic risk factors associated with sarcopenia in these patients. Patients and Methods: Sarcopenia was diagnosed by measuring handgrip strength in 166 RTR (68 females and 98 males; mean age, 37.9 ± 11.9 years). Basal metabolic rate, fat mass, free-fat mass, total body water, body mass index, and calf circumference were determined, along with blood biochemistry, vitamin D levels, and glomerular filtration rate. Results: Among 166 patients, sarcopenia was present in 34 (20.5%). Handgrip, basal metabolic rate, free fat mass, and total body water were significantly lower in patients with sarcopenia in comparison with those without sarcopenia. There were no differences between patients with and without sarcopenia in terms of mean time since transplantation, the presence of diabetes mellitus, hypertension, coronary artery disease, hyperlipidemia, glomerular filtration rate, and body mass index. Univariate analysis revealed significant differences between patients with and without sarcopenia with respect to age (mean of 43.70 ± 13.97 and 36.37 ± 10.82 years, respectively; P = 0.007) and 25-OH vitamin D levels (median (IQR) of 12 (2-39) and 17.70 (3-68) μg/L, respectively; P = 0.024). There was a statistically significant positive correlation between vitamin D levels and handgrip strength (r = 0.334; P < 0.001). Multivariate regression analysis determined that age was an independent predictive variable of sarcopenia in RTR (β = 1.060; 95% CI, 1.017-1.105; and P = 0.006). Conclusions: Chronic renal disease contributes to sarcopenia, which may develop at an earlier age in RTR.

The Effect of Hemodialysis on Cardiac Enzyme Levels and Echocardiographic Parameters

Background Cardiac troponins are specific and sensitive markers of myocardial damage. Troponin levels may increase without an obvious active cardiac disease in hemodialysis patients. In this study, we aimed to investigate the effect of a single hemodialysis session on echocardiographic parameters and cardiac enzyme levels, including cTn-I, creatine phosphokinase (CPK), and creatine kinase-MB (CK-MB). Patients and methods Forty patients under chronic hemodialysis treatment enrolled in this prospective study. All the patients had a physical examination and underwent echocardiography before and after hemodialysis. cTn-I, CPK and CK-MB levels were also determined before and after hemodialysis in all patients. Results Post-dialysis cTn-I levels were significantly higher compared to pre-dialysis levels (p = 0.03). cTn-I levels increased in 26 patients, did not change in 1 patient and decreased in 13 patients after hemodialysis when compared to the values determined before hemodialysis. There was no significant increase in CPK and CK-MB levels after dialysis. Statistically significant changes were detected in the end-systolic diameter of the left ventricle, end-diastolic diameter of left ventricle, ejection fraction, diameter of the left atrium, diameter of the right atrium, pulmonary artery pressure and end-diastolic diameter of the right ventricle. However, there was no significant relation between these echocardiographic changes and ultrafiltration volume, blood flow rate, age, and gender. Conclusions Hemodialysis leads to an increase in cTnI levels. However, the effect of increased cTnI levels on survival rates in hemodialysis patients with underlying coronary artery disease has not yet been determined. Prospective multi-center studies with large sample size are required to clarify this issue.