Plasma FGF21 Concentration in Kidney Transplant Patients-Results from Prospective and Cross-Sectional Studies.

Background/Objectives: Fibroblast growth factor 21 (FGF21) is a protein hormone involved in physiological conditions in the regulation of energy expenditure and several metabolic processes. The aim of this present study was to analyze the effect of successful kidney transplantations on the plasma FGF21 concentration and to study the factors which may influence plasma FGF21 concentration in patients in long time after kidney transplantation. Methods: This study consisted of two independent parts. The first part was a prospective observation of CKD patients in stage 5 before and then on the 14th and 30th day and 6 months after kidney transplantation. The second part of this study was the cross-sectional study completed in patients at least one year after kidney transplantation and the control group. In CKD patients directly before and during the early period after KTx, plasma FGF21 concentrations were measured four times (immediately before and 14 and 30 days and 6 months after KTx). In patients long time after kidney transplantation and in healthy subjects, plasma FGF21 concentration was measured once. Results: Forty patients with chronic kidney disease (CKD) who were either directly before or within the early period after kidney transplantation (KTx), 184 patients longtime after KTx and 50 healthy subjects were enrolled into this study. In CKD patients at the stage directly before receiving a KTx, the mean plasma FGF21 concentration was significantly higher than in the healthy subjects [1013.0 pg/mL versus 239.5 pg/mL, p < 0.001]. At 14, 30 days, and 6 months after the KTx, a significant decrease of plasma FGF21 was observed, with values of 322.5 pg/mL; 355.0 pg/mL; and 344.0 pg/mL (p < 0.001), respectively]. In patients long time after KTx, a negative correlation was found between the plasma FGF21 concentration and the estimated glomerular filtration rate and a positive correlation was found between the plasma FGF21 concentration and the BMI, the serum concentration of triglycerides, insulin, interleukin-6, CRP, and cystatin C. Conclusions: The plasma FGF21 concentration in patients with end-stage renal disease is higher than in healthy subjects and significantly decreases after a successful KTx. The plasma FGF21 concentration measured by ELISA in patients long time after kidney transplantation seems to be related to the degree of kidney function impairment and their metabolic status. The kidneys appear to be one of the main organs involved in the biodegradation and/or elimination of FGF21.

Prevalence of hypokalemia in older persons: results from the PolSenior national survey.

PURPOSE: Hypokalemia is one of the most common electrolyte disturbances in clinical practice. There are only a few epidemiological studies analyzing the occurrence of hypokalemia in older persons. The aim of the study was to determine the prevalence of hypokalemia in the Polish older population. METHODS: Serum potassium concentration was estimated in 4654 participants (2270 females and 2384 males, mean age 76.5 [11.0] years), who participated in the PolSenior study. Hypokalemia was defined as serum potassium concentration below 3.5 mmol/L. Hypokalemia was found in 39 participants (0.84%) and was significantly more frequent among females (28 females = 1.23% and 11 males = 0.46%; p = 0.003). The prevalence of hypokalemia was not related to age. Among 3303 participants suffering from arterial hypertension, 1093 were treated with potassium-losing diuretics. RESULTS: Hypokalemia was significantly more frequent among hypertensive than normotensive older participants (1.06 vs. 0.30% respectively; p = 0.007) and among hypertensive participants treated with potassium losing diuretics than ones untreated with these drugs (1.96 vs. 0.46% respectively; p < 0.001). In hypertensive participants, the prevalence of hypokalemia did not depend significantly on oral supplementation of potassium (1.92 and 0.98% respectively, NS). None of 81 participants using laxative agents presented hypokalemia. CONCLUSIONS: This study demonstrates that: older age seems not to appear to be a significant risk factor of hypokalemia. Hypokalemia is more often found in the older hypertensive patients treated with potassium losing diuretics, and prevention of diuretic-induced hypokalemia with oral supplementation of potassium seems to be insufficient.

Is Metabolic Acidosis a Novel Risk Factor for a Long-Term Graft Survival in Patients after Kidney Transplantation?

BACKGROUND: Results of both experimental and clinical studies suggest that metabolic acidosis (MA) contributes to the progression of chronic kidney disease (CKD) and mortality in CKD patients. It is unknown whether the same relationship exists in kidney transplantation (KTx) patients. The aim of this observational study was to examine this relationship between MA and both mortality and renal outcomes in patients after KTx. METHODS: Four hundred eighty-six (290 male; 196 female) patients aged 48 ± 12 years, at least 1 year after KTx, were analyzed. Blood HCO3- was measured, and patients were then observed over 3 years. MA was defined as the blood HCO3- concentration <22 mmol/L. The end points of survival analysis were death and initiation of dialysis therapy. In patients who did not reach the above-mentioned end points, the difference between final (after 3 years of follow-up) and initial estimated glomerular filtration rate (eGFR) was calculated. RESULTS: MA was initially diagnosed in 57 (12%) patients after KTx. Three-year patient survival was 89.5% in the MA group and 97.4% in the non-MA group (p = 0.001). Three-year graft survival was 73.7% for patients with MA and 93.0% for patients without MA (p < 0.001). In patients with MA who did not reach study end points, blood bicarbonate concentration at baseline correlated positively with a change in eGFR (R = 0.48, p = 0.002, n = 36). Such a correlation was not found in patients without MA (n = 388). CONCLUSIONS: (1) MA significantly increases the risk of mortality in patients after KTx. (2) The intensity of MA may be associated with progression of transplanted kidney dysfunction in KTx patients.

Changes in Office Blood Pressure Control, Augmentation Index, and Liver Steatosis in Kidney Transplant Patients after Successful Hepatitis C Infection Treatment with Direct Antiviral Agents.

Hepatitis C virus (HCV) infection in kidney transplant recipients (KTRs) can be successfully treated with direct antiviral agents (DAA). The aim of our study was to analyze different measures of vascular function during and after the DAA treatment. As we have observed the improvement of blood pressure (BP) control in some individuals, we have conducted an analysis of potential explanatory mechanisms behind this finding. Twenty-eight adult KTRs were prospectively evaluated before and 15 months after start of DAA therapy. Attended office BP (OBP), augmentation index (AIx), pulse wave velocity (PWV), flow-mediated dilation (FMD), liver stiffness measurement (LSM), and liver steatosis assessment (controlled attenuation parameter (CAP)) were measured. In half of the patients, improvement of OBP control (decline of systolic BP by at least 20 mmHg or reduction of the number of antihypertensive drugs used) and parallel central aortic pressure parameters, including AIx, was observed. There was a significant decrease in CAP mean values (241 ± 54 vs. 209 ± 30 dB/m, p < 0.05) only in patients with OBP control improvement. Half of our KTRs cohort after successful HCV eradication noted clinically important improvement of both OBP control and central aortic pressure parameters, including AIx. The concomitant decrease of liver steatosis was observed only in the subgroup of patients with improvement of blood pressure control.

Metabolic acidosis in kidney transplant recipients.

Introduction Metabolic acidosis (MA) may accelerate the progression of chronic kidney disease (CKD) and is an important risk factor for increased mortality in CKD patients. The clinical value of MA in kidney transplant (KTx) recipients has not been extensively studied so far. Objectives The aim of this clinical single­­center case­­control study was to assess the prevalence of MA in KTx recipients in comparison with CKD patients and to identify pathogenic factors for MA in KTx recipients. Patients and methods Venous blood concentrations of bicarbonate (HCO3-) and blood hemoglobin concentrations were measured in 500 KTx recipients and 500 CKD patients matched for sex, age, and estimated glomerular filtration rate (eGFR). None of these patients received alkali treatment before the study. MA was diagnosed in KTx recipients with HCO3- levels lower than 22 mmol/l. Results The prevalence of MA was lower in KTx recipients than in CKD patients (12.0% vs 19.6%; P = 0.001). In both groups, the prevalence increased with progression of CKD stages (P <0.001 for trend) and was higher in patients with anemia. In a multivariable analysis, hemoglobin concentrations correlated independently with eGFR and HCO3- in KTx recipients (ß = 0.314, P <0.001 and ß = 0.274, P <0.001, respectively). Similar correlations were observed in CKD patients (ß = 0.273, P <0.001 and ß = 0.123, P = 0.006, respectively). Conclusions Our study revealed that the prevalence of MA is lower in KTx recipients than in CKD patients. Moreover, in KTx recipients, blood bicarbonate concentrations are related to kidney function and blood hemoglobin concentrations.

Arterial stiffness but not endothelial dysfunction is associated with multidrug antihypertensive therapy and nondipper blood pressure pattern in kidney transplant recipients.

Vascular injury related to chronic kidney disease results in increased arterial stiffness and endothelial dysfunction which may affect arterial blood pressure (BP) and influence patient and graft survival in kidney transplant recipients (KTRs).This cross-sectional study aims to elucidate the relationship between the above-mentioned measures of vascular damage and effectiveness of antihypertensive treatment in KTR.One hundred forty-five KTRs 7.6 ±â€Š2.7 years after transplantation were enrolled in our study. Pulse wave velocity (PWV), flow-mediated dilation (FMD), and nitroglycerin-mediated dilation (NMD) were measured, and 24-hour ambulatory BP monitoring was performed.Overall, there were 62 patients with well-controlled or borderline BP and 83 subjects who did not achieve target BP despite antihypertensive treatment. Patients with suboptimal BP control were characterized by greater PWV (median 9.6/interquartile range: 3.9 vs 8.0/3.3 m/s, P = .002), but borderline lower FMD (8.4% ±â€Š5.0% vs 9.9% ±â€Š5.7%; P = .09) as compared with the group with better BP control. When patients were allocated to subgroups based on the number of current antihypertensive medications, no differences in FMD and NMD were found. However, a significant trend was observed for higher PWV values and decreased proportion of dippers along with the increasing number of drugs. PWV, diabetes, and total cholesterol level, but not FMD or NMD, were explanatory variables for systolic BP in multivariate analysis.Arterial stiffness but not endothelial dysfunction is associated with suboptimal BP control in stable KTRs. Less efficient antihypertensive treatment appears to be caused by inadequate control of nocturnal BP.

Chronic kidney disease and the aging population.

Along with instant aging of the world population the prevalence of chronic kidney disease is constantly growing. Over the past decade, the largest increase in the incidence of end-stage CKD was observed especially among subjects aged 80 and over. Realizing that renal replacement therapy is a heavy burden on health care it is critical to prevent end-stage kidney disease. To do so the risk and predisposing factors leading to development of renal failure have to be recognized. Among them are comorbidities such as diabetes, hypertension significantly associated with elderly, but also numerous of socioeconomics aspects. As the mean age of all populations is constantly increasing, reducing the risk of CKD in the elderly subjects is one of the most important challenge of modern nephrology.