Investigation of the effects of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on anemia in patients with normal or mildly low glomerular filtration rate

Background/aim: The relationship between the activation of the renin-angiotensin system and the increase in erythropoiesis has been shown in many studies. In addition, the use of angiotensin converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARB) has been reported to reduce hemoglobin levels in various patient groups at risk for secondary erythrocytosis/polycythemia. The aim of our study is to investigate whether there is a change in hemoglobin levels after starting ACEIs or ARBs in patients who have not used them before. Materials and methods: Three hundred and fifty-one patients who were started on renin angiotensin aldosterone system (RAAS) blockers were evaluated retrospectively. None of the patients had anemia before starting RAAS blockers. A median of 6 (4­12) months after the start of the drug, complete blood count and kidney function tests were evaluated. Hemoglobin values before and after the start of the drug were compared statistically. Results: A statistically significant decrease in mean Hb value was found after starting ACEIs or ARBs (14.39± 1.29 g/dL vs 13.98 ± 1.36 g/dL, p < 0.001). The decrease in control Hb values was higher in the ARB group than in the ACEI group (­0.53 ± 0.06 g/dL vs ­0.29 ± 0.06 g/dL, p < 0.001). Conclusion: A significant decrease in mean Hb level was detected in the first year following the first administration of ACEIs or ARBs.

Relationship between renal volume and atherosclerosis in nondiabetic hypertensive patients with normal glomerular filtration rate.

Background: The association between cystatin C (CysC) and atherosclerosis has been shown in numerous studies in hypertensive patients and in various patient groups with high cardiovascular risk. The study examining the association between renal volume and atherosclerosis is very limited. This study aimed to investigate whether there is an association between the presence of atherosclerosis with CysC and renal volume in hypertensive patients.Methods: 133 hypertensive patients and 80 healthy volunteers were evaluated. CysC level was studied in the blood sample taken from all participants. Carotid intima media thickness (CIMT) and renal volume were measured with ultrasound always by the same radiologist. Laboratory findings, CysC, CIMT, and renal volume measurements of the groups were compared statistically.Results: There was no significant difference in mean renal volume values between hypertension and control groups. There was no significant correlation between renal volume with albuminuria and proteinuria. CIMT was significantly higher in hypertension group than in control group (p = .003). There was a significant correlation between renal volume and CIMT, which is an indicator of subclinical atherosclerosis (r = 0.213, p = .001). Renal volume was found to be an independent predictor of CIMT when corrected with variables such as age, BMI, serum LDL-cholesterol level, creatinine, CysC, and albumin-to-creatinine ratio.Conclusion: Ultrasonographic renal volume measurement, which is easy to perform and does not take a long time, can be a useful method for predicting the presence of atherosclerosis in hypertensive patients with GFR >60 ml/min.

Renal function improves with the treatment of hypothyroidism.

BACKGROUND: It has been known that thyroid hormones may affect renal function. In this study, we aimed to investigate the effect of levothyroxine replacement on renal function in hypothyroid patients before and after treatment. METHODS: We retrospectively investigated free T3 (fT3), free T4 (fT4), TSH, creatinine, and eGFR measurements during both hypothyroid and euthyroid states of hypothyroid patients. The eGFR was calculated using the simplified Modification of Diet in Renal Disease formula. RESULTS: fT3, fT4, and eGFR measurements increased, meanwhile creatinine and TSH levels decreased significantly after euthyroidism was achieved with levothyroxine treatment (p < 0.0001 for all). The correlation analyses revealed that ∆creatinine and ∆TSH levels were significantly correlated before and after levothyroxine treatment (r: 0.288, p < 0.0001). ∆eGFR and ∆TSH levels were significantly correlated before and after LT4 treatment (r: -0.272, p < 0.0001). CONCLUSION: In this study, we evaluated creatinine and eGFR levels in patients with hypothyroidism and found out that renal function improved in most patients after euthyroidism was achieved. In some patients, above-normal creatinine levels completely returned to normal once the patients became euthyroid.

HFE gene mutation is a risk factor for tissue iron accumulation in hemodialysis patients.

INTRODUCTION: HFE gene mutations are responsible from iron overload in general population. Studies in hemodialysis patients investigated the effect of presence of HFE gene mutations on serum ferritin and transferrin saturation (TSAT) with conflicting results. However effect of HFE mutations on iron overload in hemodialysis patients was not previously extensively studied. METHODS: 36 hemodialysis patients (age 51.3 ± 15.6, (18/18) male/female) and 44 healthy control subjects included in this cross sectional study. Hemoglobin, ferritin, TSAT in the preceding 2 years were recorded. Iron and erythropoietin (EPO) administered during this period were calculated. Iron accumulation in heart and liver was detected by MRI. Relationship between HFE gene mutation, hemoglobin, iron parameters and EPO doses, and tissue iron accumulation were determined. FINDINGS: Iron overload was detected in nine (25%) patients. Hemoglobin, iron parameters, weekly EPO doses, and monthly iron doses of patients with and without iron overload were similar. There was no difference between control group and hemodialysis patients with respect to the prevalence of HFE gene mutations. Iron overload was detected in five of eight patients who had HFE gene mutations, but iron overload was present in 4 of 28 patients who had no mutations (P = 0.01). Hemoglobin, iron parameters, erythropoietin, and iron doses were similar in patients with and without gene mutations. HFE gene mutations remained the main determinant of iron overload after multivariate logistic regression analysis (P = 0.02; OR, 11.6). DISCUSSION: Serum iron parameters were not adequate to detect iron overload and HFE gene mutation was found to be an important risk factor for iron accumulation.

Potassium abnormalities in current clinical practice: frequency, causes, severity and management.

OBJECTIVE: We aimed to investigate the prevalence and etiology of potassium abnormalities (hypokalemia and hyperkalemia) and management approaches for hospitalized patients. SUBJECTS AND METHODS: Over a 4-month period, all hospitalized patients at Hacettepe University Medical Faculty Hospitals who underwent at least one measurement of serum potassium during hospitalization were included. Data on serum levels of electrolytes, demographic characteristics, cause(s) of hospitalization, medications, etiology of potassium abnormality and treatment approaches were obtained from the hospital records. RESULTS: Of the 9,045 hospitalized patients, 1,265 (14.0%) had a serum potassium abnormality; 604 (6.7%) patients had hypokalemia and 661 (7.30%) had hyperkalemia. In the hypokalemic patients, the most important reasons were gastrointestinal losses in 555 (91.8%) patients and renal losses in 252 (41.7%) patients. The most frequent treatment strategies were correcting the underlying cause and replacing the potassium deficit. Of the 604 hypokalemic patients, 319 (52.8%) were normokalemic at hospital discharge. The most common reason for hyperkalemia was treatment with renin-angiotensin-aldosterone system blockers in 228 (34.4%) patients, followed by renal failure in 191 (28.8%). Two hundred and ninety-eight (45.0%) patients were followed without any specific treatment. Of the 661 hyperkalemic patients, 324 (49.0%) were normokalemic at hospital discharge. CONCLUSION: This study showed a high prevalence of potassium imbalance among hospitalized patients. Although most of the potassium abnormalities were mild/moderate, approximately half of the patients treated for hypokalemia or hyperkalemia were discharged from the hospital with ongoing dyskalemia.

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.

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 m(2); (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.

Effects of lowering dialysate sodium on flow-mediated dilatation in patients with chronic kidney disease.

OBJECTIVE: This study examined the effects of low dialysate sodium on endothelial dysfunction (ED) as measured by flow-mediated dilatation (FMD) of brachial artery in haemodialysis (HD) patients. METHODS: Thirty HD patients (17 men; mean age: 48.4 ± 17.8 years) were studied. Subjects underwent two consecutive 6-week HD periods. Dialysate sodium was 143 mEq/L in the first period (standard Na HD) and 137 mEq/L in the second period (low Na HD). After each period, we performed FMD, echocardiographic evaluation and 24-h ambulatory blood pressure monitoring (ABPM). Interdialytic weight gain (IDWG), levels of pre- and post-dialysis blood pressure (BP), and dialysis-related symptoms were monitored during the study. RESULTS: Per cent FMD was significantly greater (P < 0.05) after low Na HD (9.3 ± 6.2) compared with standard Na HD (5.7 ± 6.2). IDWG was significantly lower during low Na HD (2.35 ± 0.86 kg versus 2.71 ± 0.89 kg; P < 0.001). BP control was improved during low Na HD, as assessed by ABPM (128.2/77.5 mmHg versus 132.4/80.8 mmHg). Dialysis-related symptoms were more frequent during low Na HD (P < 0.05). There was no change in left ventricular mass after reducing dialysate sodium. CONCLUSIONS: Reducing dialysate sodium concentration reduced ED, and provided better control of IDWG and BP, but increased dialysis-related symptoms.

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.